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TMTC4 transmembrane O-mannosyltransferase targeting cadherins 4 [ Homo sapiens (human) ]

Gene ID: 84899, updated on 2-Nov-2024

Summary

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Official Symbol
TMTC4provided by HGNC
Official Full Name
transmembrane O-mannosyltransferase targeting cadherins 4provided by HGNC
Primary source
HGNC:HGNC:25904
See related
Ensembl:ENSG00000125247 MIM:618203; AllianceGenome:HGNC:25904
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
DFNB122
Summary
This gene encodes a transmembrane protein that belongs to family of proteins containing an N-terminal transmembrane domain and a C-terminal tetratricopeptide repeat (TPR) domain. TPR domains mediate protein-protein interactions in various cellular processes, such as synaptic vesicle fusion, protein folding, and protein translocation. A pseudogene of this gene has been defined on chromosome 5. [provided by RefSeq, Apr 2017]
Expression
Ubiquitous expression in brain (RPKM 8.0), testis (RPKM 5.8) and 25 other tissues See more
Orthologs
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Genomic context

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See TMTC4 in Genome Data Viewer
Location:
13q32.3
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (100603625..100675075, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (99818881..99890298, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (101255879..101327049, complement)

Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene propionyl-CoA carboxylase subunit alpha Neighboring gene uncharacterized LOC107984574 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:101144770-101145270 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:101145271-101145771 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:101154747-101155384 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:101161543-101162161 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr13:101162162-101162780 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:101162781-101163398 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:101169316-101170040 Neighboring gene PCCA antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:101171491-101172156 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:101177366-101177888 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:101182623-101183592 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7960 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:101198945-101199623 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:101197474-101198196 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:101196750-101197473 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:101199624-101200301 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5477 Neighboring gene ribosomal protein S26 pseudogene 47 Neighboring gene gamma-glutamylamine cyclotransferase Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:101279471-101279992 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:101311281-101311784 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5478 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:101325425-101326314 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5479 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5480 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7961 Neighboring gene cytochrome c oxidase subunit 5B pseudogene 6 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:101350546-101351126 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr13:101390455-101391100 Neighboring gene NALCN antisense RNA 1 Neighboring gene ARF GTPase 4 pseudogene 3 Neighboring gene Sharpr-MPRA regulatory region 9290 Neighboring gene long intergenic non-protein coding RNA 411

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Transmembrane and Tetratricopeptide Repeat Containing 4 Is a Novel Diagnostic Marker for Prostate Cancer with High Specificity and Sensitivity. Makboul R, et al. Cells, 2021 Apr 27. PMID 33925440, Free PMC Article
  2. TMTC4 is a hair cell-specific human deafness gene. Li J, et al. JCI Insight, 2023 Dec 22. PMID 37943620, Free PMC Article
  3. Conserved sequence motifs in human TMTC1, TMTC2, TMTC3, and TMTC4, new O-mannosyltransferases from the GT-C/PMT clan, are rationalized as ligand binding sites. Eisenhaber B, et al. Biol Direct, 2021 Jan 12. PMID 33436046, Free PMC Article
  4. Discovery of an O-mannosylation pathway selectively serving cadherins and protocadherins. Larsen ISB, et al. Proc Natl Acad Sci U S A, 2017 Oct 17. PMID 28973932, Free PMC Article
  5. Deletion of Tmtc4 activates the unfolded protein response and causes postnatal hearing loss. Li J, et al. J Clin Invest, 2018 Nov 1. PMID 30188326, Free PMC Article

See all (28) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. TMTC4 is a hair cell-specific human deafness gene.
    Title: TMTC4 is a hair cell-specific human deafness gene.
  2. Transmembrane and Tetratricopeptide Repeat Containing 4 Is a Novel Diagnostic Marker for Prostate Cancer with High Specificity and Sensitivity.
    Title: Transmembrane and Tetratricopeptide Repeat Containing 4 Is a Novel Diagnostic Marker for Prostate Cancer with High Specificity and Sensitivity.
  3. Conserved sequence motifs in human TMTC1, TMTC2, TMTC3, and TMTC4, new O-mannosyltransferases from the GT-C/PMT clan, are rationalized as ligand binding sites.
    Title: Conserved sequence motifs in human TMTC1, TMTC2, TMTC3, and TMTC4, new O-mannosyltransferases from the GT-C/PMT clan, are rationalized as ligand binding sites.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Hearing loss, autosomal recessive 122
MedGen: CN376840 OMIM: 620714 GeneReviews: Not available
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ14624, FLJ22153, FLJ42608

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATPase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables dolichyl-phosphate-mannose-protein mannosyltransferase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables mannosyltransferase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in endoplasmic reticulum unfolded protein response IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in outer hair cell apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of endoplasmic reticulum calcium ion concentration IEA
Inferred from Electronic Annotation
more info
  
involved_in protein O-linked mannosylation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein O-linked mannosylation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in sensory perception of sound IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
is_active_in endoplasmic reticulum IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
located_in membrane IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
protein O-mannosyl-transferase TMTC4
Names
transmembrane and TPR repeat-containing protein 4
transmembrane and tetratricopeptide repeat containing 4
NP_001073137.1
NP_001273382.1
NP_001337500.1
NP_001337501.1
NP_001337503.1
NP_001337505.1
NP_001337506.1
NP_116202.2
XP_011519424.1
XP_047286661.1
XP_047286662.1
XP_054231045.1
XP_054231046.1
XP_054231047.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_053145.1 RefSeqGene

    Range
    5299..76469
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001079669.4 → NP_001073137.1  protein O-mannosyl-transferase TMTC4 isoform 2

    See identical proteins and their annotated locations for NP_001073137.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, has multiple coding region differences, and initiates translation at a downstream start codon, compared to variant 4. The encoded isoform (2) is shorter than isoform 4. Both variants 2 and 5 encode the same isoform (2).
    Source sequence(s)
    AL359085, AW513848, BX647956
    Consensus CDS
    CCDS41904.1
    UniProtKB/Swiss-Prot
    A6NLI7, B7Z666, Q5T4D3, Q5T4D4, Q5T4D5, Q5T4D6, Q8WV63, Q96SU8
    UniProtKB/TrEMBL
    A8K2T0
    Related
    ENSP00000365408.3, ENST00000376234.7
    Conserved Domains (3) summary
    COG0457
    Location:481 → 717
    TPR; Tetratricopeptide (TPR) repeat [General function prediction only]
    sd00006
    Location:482 → 510
    TPR; TPR repeat [structural motif]
    pfam08409
    Location:294 → 366
    DUF1736; Domain of unknown function (DUF1736)

  2. NM_001286453.3 → NP_001273382.1  protein O-mannosyl-transferase TMTC4 isoform 3

    See identical proteins and their annotated locations for NP_001273382.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, contains multiple differences in the 5' coding region, and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
    Source sequence(s)
    AF339792, AK299859, AL359085, AW513848, DC377683
    Consensus CDS
    CCDS66575.1
    UniProtKB/TrEMBL
    A8K2T0
    Related
    ENSP00000365409.2, ENST00000328767.9
    Conserved Domains (7) summary
    smart00028
    Location:473 → 506
    TPR; Tetratricopeptide repeats
    sd00006
    Location:371 → 399
    TPR; TPR repeat [structural motif]
    pfam00515
    Location:439 → 472
    TPR_1; Tetratricopeptide repeat
    pfam07719
    Location:371 → 404
    TPR_2; Tetratricopeptide repeat
    pfam08409
    Location:181 → 255
    DUF1736; Domain of unknown function (DUF1736)
    pfam13414
    Location:370 → 436
    TPR_11; TPR repeat
    pfam13431
    Location:393 → 426
    TPR_17; Tetratricopeptide repeat

  3. NM_001350571.2 → NP_001337500.1  protein O-mannosyl-transferase TMTC4 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) represents the longest transcript and encodes the longest isoform (4).
    Source sequence(s)
    AL359085
    UniProtKB/TrEMBL
    A8K2T0
    Conserved Domains (3) summary
    COG0457
    Location:558 → 794
    TPR; Tetratricopeptide (TPR) repeat [General function prediction only]
    sd00006
    Location:559 → 587
    TPR; TPR repeat [structural motif]
    pfam08409
    Location:369 → 443
    DUF1736; Domain of unknown function (DUF1736)

  4. NM_001350572.2 → NP_001337501.1  protein O-mannosyl-transferase TMTC4 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR, has multiple coding region differences, and initiates translation at a downstream start codon, compared to variant 4. The encoded isoform (2) is shorter than isoform 4. Both variants 2 and 5 encode the same isoform (2).
    Source sequence(s)
    AL359085
    Consensus CDS
    CCDS41904.1
    UniProtKB/Swiss-Prot
    A6NLI7, B7Z666, Q5T4D3, Q5T4D4, Q5T4D5, Q5T4D6, Q8WV63, Q96SU8
    UniProtKB/TrEMBL
    A8K2T0
    Conserved Domains (3) summary
    COG0457
    Location:481 → 717
    TPR; Tetratricopeptide (TPR) repeat [General function prediction only]
    sd00006
    Location:482 → 510
    TPR; TPR repeat [structural motif]
    pfam08409
    Location:294 → 366
    DUF1736; Domain of unknown function (DUF1736)

  5. NM_001350574.2 → NP_001337503.1  protein O-mannosyl-transferase TMTC4 isoform 5

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) differs in the 5' UTR and 5' coding region, and initiates translation at a downstream start codon, compared to variant 4. The encoded isoform (5) is has a shorter and distinct N-terminus compared to isoform 4.
    Source sequence(s)
    AL359085
    UniProtKB/TrEMBL
    A8K2T0
    Conserved Domains (3) summary
    COG0457
    Location:539 → 775
    TPR; Tetratricopeptide (TPR) repeat [General function prediction only]
    sd00006
    Location:540 → 568
    TPR; TPR repeat [structural motif]
    pfam08409
    Location:350 → 424
    DUF1736; Domain of unknown function (DUF1736)

  6. NM_001350576.2 → NP_001337505.1  protein O-mannosyl-transferase TMTC4 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) lacks an alternate in-frame exon in the 5' coding region, compared to variant 4. The encoded isoform (6) is shorter than isoform 4.
    Source sequence(s)
    AL359085
    UniProtKB/TrEMBL
    A8K2T0
    Conserved Domains (3) summary
    COG0457
    Location:498 → 734
    TPR; Tetratricopeptide (TPR) repeat [General function prediction only]
    sd00006
    Location:499 → 527
    TPR; TPR repeat [structural motif]
    pfam08409
    Location:313 → 383
    DUF1736; Domain of unknown function (DUF1736)

  7. NM_001350577.2 → NP_001337506.1  protein O-mannosyl-transferase TMTC4 isoform 7

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8) differs in the 5' UTR, has multiple coding region differences, and initiates translation at a downstream start codon, compared to variant 4. The encoded isoform (7) is shorter than isoform 4.
    Source sequence(s)
    AL359085
    UniProtKB/TrEMBL
    A8K2T0
    Conserved Domains (3) summary
    COG0457
    Location:479 → 715
    TPR; Tetratricopeptide (TPR) repeat [General function prediction only]
    sd00006
    Location:480 → 508
    TPR; TPR repeat [structural motif]
    pfam08409
    Location:294 → 364
    DUF1736; Domain of unknown function (DUF1736)

  8. NM_032813.5 → NP_116202.2  protein O-mannosyl-transferase TMTC4 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) lacks an alternate in-frame exon in the 5' coding region, compared to variant 4. The encoded isoform (1) is shorter than isoform 4.
    Source sequence(s)
    AK056409, AL359085, AW513848, BG830268, CV029196, DA368450
    Consensus CDS
    CCDS9497.2
    UniProtKB/TrEMBL
    A8K2T0
    Related
    ENSP00000343871.5, ENST00000342624.10
    Conserved Domains (7) summary
    smart00028
    Location:603 → 636
    TPR; Tetratricopeptide repeats
    sd00006
    Location:501 → 529
    TPR; TPR repeat [structural motif]
    pfam00515
    Location:569 → 602
    TPR_1; Tetratricopeptide repeat
    pfam07719
    Location:501 → 534
    TPR_2; Tetratricopeptide repeat
    pfam08409
    Location:311 → 385
    DUF1736; Domain of unknown function (DUF1736)
    pfam13414
    Location:500 → 566
    TPR_11; TPR repeat
    pfam13431
    Location:523 → 556
    TPR_17; Tetratricopeptide repeat

RNA

  1. NR_146794.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (9) lacks two alternate exons in the 5' region and contains an alternate exon in the 3' region, compared to variant 4. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AL359085

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

    Range
    100603625..100675075 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047430706.1 → XP_047286662.1  protein O-mannosyl-transferase TMTC4 isoform X3

  2. XM_011521122.4 → XP_011519424.1  protein O-mannosyl-transferase TMTC4 isoform X1

    See identical proteins and their annotated locations for XP_011519424.1

    UniProtKB/TrEMBL
    A8K2T0
    Conserved Domains (3) summary
    COG0457
    Location:558 → 794
    TPR; Tetratricopeptide (TPR) repeat [General function prediction only]
    sd00006
    Location:559 → 587
    TPR; TPR repeat [structural motif]
    pfam08409
    Location:369 → 443
    DUF1736; Domain of unknown function (DUF1736)

  3. XM_047430705.1 → XP_047286661.1  protein O-mannosyl-transferase TMTC4 isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060937.1 Alternate T2T-CHM13v2.0

    Range
    99818881..99890298 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054375070.1 → XP_054231045.1  protein O-mannosyl-transferase TMTC4 isoform X1

  2. XM_054375072.1 → XP_054231047.1  protein O-mannosyl-transferase TMTC4 isoform X3

  3. XM_054375071.1 → XP_054231046.1  protein O-mannosyl-transferase TMTC4 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q5T4D3.2 GenPept UniProtKB/Swiss-Prot:Q5T4D3

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