TMCO1 transmembrane and coiled-coil domains 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TMCO1provided by HGNC
Official Full Name: transmembrane and coiled-coil domains 1provided by HGNC
Primary source: HGNC:HGNC:18188
See related: Ensembl:ENSG00000143183 MIM:614123; AllianceGenome:HGNC:18188
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: PCIA3; TMCC4; CFSMR1; HP10122; PNAS-136
Summary: This locus encodes a transmembrane protein. Mutations at this locus have been associated with craniofacial dysmorphism, skeletal anomalies, and cognitive disability. Mutations at this locus have also been associated with open angle glaucoma blindness. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012]
Expression: Ubiquitous expression in colon (RPKM 19.0), thyroid (RPKM 18.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q24.1

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (165724291..165768922, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (165070667..165115003, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (165693528..165738159, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

TMCO1 regulates cell proliferation, metastasis and EMT signaling through CALR, promoting ovarian cancer progression and cisplatin resistance.
Title: TMCO1 regulates cell proliferation, metastasis and EMT signaling through CALR, promoting ovarian cancer progression and cisplatin resistance.
Repeat polymorphisms underlie top genetic risk loci for glaucoma and colorectal cancer.
Title: Repeat polymorphisms underlie top genetic risk loci for glaucoma and colorectal cancer.
Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome-1 in two new patients with the same homozygous TMCO1 variant and review of the literature.
Title: Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome-1 in two new patients with the same homozygous TMCO1 variant and review of the literature.
iASPP suppresses Gp78-mediated TMCO1 degradation to maintain Ca(2+) homeostasis and control tumor growth and drug resistance.
Title: iASPP suppresses Gp78-mediated TMCO1 degradation to maintain Ca(2+) homeostasis and control tumor growth and drug resistance.
A novel biallelic loss-of-function mutation in TMCO1 gene confirming and expanding the phenotype spectrum of cerebro-facio-thoracic dysplasia.
Title: A novel biallelic loss-of-function mutation in TMCO1 gene confirming and expanding the phenotype spectrum of cerebro-facio-thoracic dysplasia.
CDKN2B-AS1 can inhibit the transcription of ADAM10 via DNMT1-mediated ADAM10 DNA methylation, consequently preventing inflammatory response of atherosclerosis and promoting cholesterol efflux.
Title: Long non-coding RNA CDKN2B-AS1 reduces inflammatory response and promotes cholesterol efflux in atherosclerosis by inhibiting ADAM10 expression.
Our results demonstrate that a SNP downstream of TMCO1, rs4657473, is associated with POAG in an AA population. Our studies suggest a regulatory role for the previously POAG-associated locus near the TMCO1 gene that may affect gene expression.
Title: SNP located in an AluJb repeat downstream of TMCO1, rs4657473, is protective for POAG in African Americans.
Thus we provide evidence that cerebrofaciothoracic dysplasia (CFTD) may be more common than previously thought. The patients presented here further delineate the phenotypic spectrum of CFTD and provide evidence for a recurrent pathogenic variant in TMCO1.
Title: Cerebrofaciothoracic dysplasia: Four new patients with a recurrent TMCO1 pathogenic variant.
An essential role of TMCO1 in osteogenesis mediated by local Ca(2+)/CaMKII signaling in osteoblasts.TMCO1 levels were significantly decreased in bone from both osteoporosis patients.
Title: TMCO1-mediated Ca(2+) leak underlies osteoblast functions via CaMKII signaling.
TMCO1 recruited the PH domain and leucine-rich repeat protein phosphatase 2 (PHLPP2) to dephosphorylate pAKT1(serine 473) (S473). Mutagenesis at S60 of the TMCO1 protein released TMCO1-induced cell-cycle arrest and restored the AKT pathway in BFTC905 cells. Stable TMCO1 (wild-type) overexpression suppressed, whereas T33A and S60A mutants recovered, tumor size in xenograft mice.
Title: Transmembrane and Coiled-Coil Domain 1 Impairs the AKT Signaling Pathway in Urinary Bladder Urothelial Carcinoma: A Characterization of a Tumor Suppressor.

Submit: New GeneRIF Correction See all GeneRIFs (19)

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
Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1 MedGen: C5677021 OMIM: 213980 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Common genetic determinants of intraocular pressure and primary open-angle glaucoma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study and meta-analysis of intraocular pressure. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH69472 (e-PCR)
- UniSTS:79634

WI-14174 (e-PCR)
- UniSTS:18968

WI-16096 (e-PCR)
- UniSTS:22698

TMCO1 (e-PCR)
- UniSTS:503776

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ribosome binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in ER overload response	IDA Inferred from Direct Assay more info	PubMed
involved_in calcium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in endoplasmic reticulum calcium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in endoplasmic reticulum calcium ion homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in multi-pass transmembrane protein insertion into ER membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in ossification	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in Golgi membrane	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
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
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial membrane	IEA Inferred from Electronic Annotation more info
part_of multi-pass translocon complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: calcium load-activated calcium channel

Names: CLAC channel; Ca(2+) load-activated Ca(2+) channel; GEL complex subunit TMCO1; putative membrane protein; transmembrane and coiled-coil domain-containing protein 1; transmembrane and coiled-coil domains 4; xenogeneic cross-immune protein PCIA3

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

NG_032004.1 RefSeqGene

Range

5055..47128

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001256164.1 → NP_001243093.1 calcium load-activated calcium channel isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses two alternate in-frame splice sites in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform b), compared to isoform a.

Source sequence(s)

AI379550, AK316080, AL451074, BP257387

UniProtKB/Swiss-Prot

B2REA0, J9JIE6, O75545, Q9BZS3, Q9BZU8, Q9UM00

Related

ENSP00000480514.1, ENST00000612311.4

Conserved Domains (1) summary

pfam01956
Location:45 → 182

DUF106; Integral membrane protein DUF106
NM_001256165.1 → NP_001243094.1 calcium load-activated calcium channel isoform c

See identical proteins and their annotated locations for NP_001243094.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice site in the 5' coding region and uses a downstream start codon, compared to variant 1. The encoded isoform (c) has a shorter and distinct N-terminus, compared to isoform a.

Source sequence(s)

AI379550, AK298614, AK316080, AL451074

UniProtKB/TrEMBL

B7Z591, J3KS45

Related

ENSP00000462300.2, ENST00000481278.6

Conserved Domains (1) summary

pfam01956
Location:11 → 153

DUF106; Integral membrane protein DUF106
NM_019026.6 → NP_061899.3 calcium load-activated calcium channel isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a).

Source sequence(s)

AF070626, AL451074

Consensus CDS

CCDS1251.3

Related

ENSP00000356856.6, ENST00000367881.11

Conserved Domains (1) summary

pfam01956
Location:8 → 165

DUF106; Integral membrane protein DUF106

RNA

NR_045818.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate splice site in the 5' terminal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AI379550, AK316080, AL451074, BP257387