ALDH6A1 aldehyde dehydrogenase 6 family member A1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ALDH6A1provided by HGNC
Official Full Name: aldehyde dehydrogenase 6 family member A1provided by HGNC
Primary source: HGNC:HGNC:7179
See related: Ensembl:ENSG00000119711 MIM:603178; AllianceGenome:HGNC:7179
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: MMSDH; MMSADHA
Summary: This gene encodes a member of the aldehyde dehydrogenase protein family. The encoded protein is a mitochondrial methylmalonate semialdehyde dehydrogenase that plays a role in the valine and pyrimidine catabolic pathways. This protein catalyzes the irreversible oxidative decarboxylation of malonate and methylmalonate semialdehydes to acetyl- and propionyl-CoA. Methylmalonate semialdehyde dehydrogenase deficiency is characterized by elevated beta-alanine, 3-hydroxypropionic acid, and both isomers of 3-amino and 3-hydroxyisobutyric acids in urine organic acids. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]
Expression: Biased expression in kidney (RPKM 142.3), liver (RPKM 67.8) and 11 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q24.3

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (74056847..74084453, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (68264517..68292135, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (74523550..74551156, complement)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

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?

The downregulated drug-metabolism related ALDH6A1 serves as predictor for prognosis and therapeutic immune response in gastric cancer.
Title: The downregulated drug-metabolism related ALDH6A1 serves as predictor for prognosis and therapeutic immune response in gastric cancer.
ALDH6A1 weakens the progression of colon cancer via modulating the RAS/RAF/MEK/ERK pathway in cancer cell lines.
Title: ALDH6A1 weakens the progression of colon cancer via modulating the RAS/RAF/MEK/ERK pathway in cancer cell lines.
Identification and validation of a two-gene metabolic signature for survival prediction in patients with kidney renal clear cell carcinoma.
Title: Identification and validation of a two-gene metabolic signature for survival prediction in patients with kidney renal clear cell carcinoma.
Identification of ALDH6A1 as a Potential Molecular Signature in Hepatocellular Carcinoma via Quantitative Profiling of the Mitochondrial Proteome.
Title: Identification of ALDH6A1 as a Potential Molecular Signature in Hepatocellular Carcinoma via Quantitative Profiling of the Mitochondrial Proteome.
Results show that ALDH6A1 expression is significantly reduced in metastatic prostate cancer and represents a strong marker predicting survival, along with HSP27 and prohibitin.
Title: HSP27, ALDH6A1 and Prohibitin Act as a Trio-biomarker to Predict Survival in Late Metastatic Prostate Cancer.
ACAT1, ACACA, ALDH6A1 and MTHFD1 represent novel biomarkers in adipose tissue associated with type 2 diabetes in obese individuals.
Title: Downregulation of the acetyl-CoA metabolic network in adipose tissue of obese diabetic individuals and recovery after weight loss.
Mutation analysis in the ALDH6A1 gene can reveal a cause of 3-hydroxyisobutyric aciduria, which may present with only slightly increased urinary levels of 3-hydroxyisobutyric acid, if a patient is metabolically stable [case reports]
Title: 3-Hydroxyisobutyrate aciduria and mutations in the ALDH6A1 gene coding for methylmalonate semialdehyde dehydrogenase.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.

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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
Methylmalonate semialdehyde dehydrogenase deficiency MedGen: C3279840 OMIM: 614105 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Web-based, participant-driven studies yield novel genetic associations for common traits. 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

RH69632 (e-PCR)
- UniSTS:91714

RH92479 (e-PCR)
- UniSTS:83800

SHGC-54582 (e-PCR)
- UniSTS:47212

RH98826 (e-PCR)
- UniSTS:86149

STS-R00273 (e-PCR)
- UniSTS:5514

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	PubMed
enables malonate-semialdehyde dehydrogenase (acetylating) activity	IEA Inferred from Electronic Annotation more info
enables methylmalonate-semialdehyde dehydrogenase (acylating, NAD) activity	IBA Inferred from Biological aspect of Ancestor more info
enables methylmalonate-semialdehyde dehydrogenase (acylating, NAD) activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables methylmalonate-semialdehyde dehydrogenase (acylating, NAD) activity	ISS Inferred from Sequence or Structural Similarity more info
enables methylmalonate-semialdehyde dehydrogenase (acylating, NAD) activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in branched-chain amino acid catabolic process	TAS Traceable Author Statement more info
involved_in brown fat cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in thymine catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in thymine catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in thymine metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in valine catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in valine catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in valine metabolic process	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info
located_in mitochondrion	NAS Non-traceable Author Statement more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: methylmalonate-semialdehyde/malonate-semialdehyde dehydrogenase [acylating], mitochondrial

Names: malonate-semialdehyde dehydrogenase (acetylating); methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial; mitochondrial acylating methylmalonate-semialdehyde dehydrogenase; testicular tissue protein Li 122

NP_001265522.1

EC 1.2.1.27

NP_001265523.1

EC 1.2.1.27

NP_005580.1

EC 1.2.1.27

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_012257.2 RefSeqGene

Range

5041..32647

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001278593.2 → NP_001265522.1 methylmalonate-semialdehyde/malonate-semialdehyde dehydrogenase [acylating], mitochondrial isoform 2 precursor

Status: REVIEWED

Description

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

Source sequence(s)

AC005484, AI244036, AK294243

Consensus CDS

CCDS61501.1

UniProtKB/TrEMBL

Q53H94

Related

ENSP00000342564.4, ENST00000350259.8

Conserved Domains (1) summary

cd07085
Location:40 → 503

ALDH_F6_MMSDH; Methylmalonate semialdehyde dehydrogenase and ALDH family members 6A1 and 6B2
NM_001278594.2 → NP_001265523.1 methylmalonate-semialdehyde/malonate-semialdehyde dehydrogenase [acylating], mitochondrial isoform 3

Status: REVIEWED

Description

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

Source sequence(s)

AC005484, AI244036, AK311478

Conserved Domains (1) summary

cd07085
Location:1 → 362

ALDH_F6_MMSDH; Methylmalonate semialdehyde dehydrogenase and ALDH family members 6A1 and 6B2
NM_005589.4 → NP_005580.1 methylmalonate-semialdehyde/malonate-semialdehyde dehydrogenase [acylating], mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_005580.1

Status: REVIEWED

Description

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

Source sequence(s)

AC005484, AI244036, BC032371

Consensus CDS

CCDS9826.1

UniProtKB/Swiss-Prot

B2R609, B4DFS8, J3KNU8, Q02252, Q9UKM8

UniProtKB/TrEMBL

A0A024R6G4, Q53H94

Related

ENSP00000450436.1, ENST00000553458.6

Conserved Domains (1) summary

cd07085
Location:40 → 516

ALDH_F6_MMSDH; Methylmalonate semialdehyde dehydrogenase and ALDH family members 6A1 and 6B2