HIGD1A
protein-codingHIG1 hypoxia inducible domain family member 1A, the group of Mitochondrial respiratory chain complex assembly factors
Gene summary
Acts upstream of or within negative regulation of apoptotic process. Located in mitochondrion. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HIGD1A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014056.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 15 | 1 | 16 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 16 | 1 | 0 | 17 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_054775.2 | 3 | MANE Select | |
| Ensembl | ENSP00000319393.7 | 3 | MANE Select | |
| RefSeq | NP_001093138.1 | 4 | Standard | |
| RefSeq | NP_001093139.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of Hypoxia-inducible Factor (HIF) by oxygen
Biological Process
- cellular response to glucose starvation
- negative regulation of apoptotic process
- oxidation-reduction process
- regulation of transcription from RNA polymerase II promoter in response to hypoxia
- positive regulation of protein serine/threonine kinase activity
Cellular Component
- nucleoplasm
- mitochondrion
- mitochondrial inner membrane
- integral component of membrane
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000452906
- Coding exons
- 4
- Length
- 47355
- Individuals with no LoFs
- 124754
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 124762
- p
- 0.0000321
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.148 | 59 | 62.3 | 0.947 | 0.00000324 | 683 |
| Missense (PolyPhen) | 10 | 10.912 | 0.91645 | 165 | ||
| Synonymous | -0.251 | 21 | 19.6 | 1.07 | 0.00000107 | 203 |
| Loss of Function | 1.17 | 3 | 6.13 | 0.490 | 3.24e-7 | 73 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Proposed subunit of cytochrome c oxidase (COX, complex IV), which is the terminal component of the mitochondrial respiratory chain that catalyzes the reduction of oxygen to water. May play a role in the assembly of respiratory supercomplexes. {ECO:0000269|PubMed:22342701}.;
Recessive Scores
- pRec
- 0.246
Intolerance Scores
- LoFtool
- 0.485
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.04
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.903
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |