HIGD2A
protein-codingHIG1 hypoxia inducible domain family member 2A, the group of Mitochondrial respiratory chain complex assembly factors
Gene summary
The protein encoded by this gene is a subunit of the cytochrome c oxidase complex (complex IV), which is the terminal enzyme in the mitochondrial respiratory chain. The encoded protein is an inner mitochondrial membrane protein and is a functional ortholog of the yeast respiratory supercomplex factor 1 (Rcf1). In mouse, the orthologous protein enhances cell survival under conditions of hypoxia. [provided by RefSeq, Sep 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.0 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 HIGD2A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_138820.4. 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 | 9 | 1 | 10 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 9 | 1 | 0 | 10 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_620175.1 | 2 | MANE Select | |
| Ensembl | ENSP00000274787.2 | 2 | MANE Select | |
| Ensembl | ENSP00000767900.1 | 2 | Standard | |
| Ensembl | ENSP00000767901.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of apoptotic process
- oxidation-reduction process
Cellular Component
- mitochondrial inner membrane
- integral component of membrane
- respirasome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000274787
- Coding exons
- 2
- Length
- 1025
- Individuals with no LoFs
- 125722
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125734
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.398 | 57 | 66.1 | 0.862 | 0.00000291 | 672 |
| Missense (PolyPhen) | 17 | 18.966 | 0.89632 | 211 | ||
| Synonymous | -0.306 | 30 | 27.9 | 1.07 | 0.00000126 | 239 |
| Loss of Function | 0.939 | 1 | 2.65 | 0.378 | 1.12e-7 | 32 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000063 | 0.000062 | rare |
| Latino/Admixed American | 0.00029 | 0.00029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | 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 be involved in cytochrome c oxidase activity. May play a role in the assembly of respiratory supercomplexes. {ECO:0000269|PubMed:22342701}.;
Recessive Scores
- pRec
- 0.0768
Intolerance Scores
- LoFtool
- 0.407
- RVIS EVS
- 0.01
- RVIS percentile EVS
- 54.63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.723
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |