HIF1AN
protein-codinghypoxia inducible factor 1 subunit alpha inhibitor, the group of JmjC hydroxylases
Gene summary
Enables several functions, including 2-oxoglutarate-dependent dioxygenase activity; NF-kappaB binding activity; and transition metal ion binding activity. Involved in negative regulation of Notch signaling pathway and positive regulation of myoblast differentiation. Located in cytosol; nucleoplasm; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~30.9 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 HIF1AN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017902.3. 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 | 1 | 1 | ||||
| missense | 24 | 24 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 27 | 0 | 1 | 28 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060372.2 | 8 | MANE Select | |
| Ensembl | ENSP00000299163.4 | 8 | MANE Select | |
| Ensembl | ENSP00000432791.1 | 2 | Standard | |
| Ensembl | ENSP00000433360.2 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| hif1an | Danio rerio | Structure: angiogenic sprout Quality: mislocalised abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glutaminolysis and Cancer
- miR-148a-miR-31-FIH1-HIF1α-Notch signaling in glioblastoma
- Photodynamic therapy-induced HIF-1 survival signaling
- Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha
- Regulation of Hypoxia-inducible Factor (HIF) by oxygen
Biological Process
- peptidyl-histidine hydroxylation
- peptidyl-aspartic acid hydroxylation
- peptidyl-asparagine hydroxylation
- positive regulation of myoblast differentiation
- negative regulation of Notch signaling pathway
Molecular Function
- Notch binding
- iron ion binding
- protein binding
- zinc ion binding
- 2-oxoglutarate-dependent dioxygenase activity
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000299163
- Coding exons
- 8
- Length
- 30927
- Individuals with no LoFs
- 125735
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125748
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.02 | 111 | 189 | 0.587 | 0.00000912 | 2315 |
| Missense (PolyPhen) | 25 | 73.175 | 0.34164 | 919 | ||
| Synonymous | 0.781 | 64 | 72.5 | 0.883 | 0.00000388 | 629 |
| Loss of Function | 3.07 | 6 | 21.2 | 0.282 | 0.00000109 | 227 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000067 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydroxylates HIF-1 alpha at 'Asn-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300- interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation. {ECO:0000269|PubMed:12042299, ECO:0000269|PubMed:12080085, ECO:0000269|PubMed:17003112, ECO:0000269|PubMed:17573339, ECO:0000269|PubMed:18299578, ECO:0000269|PubMed:19245366, ECO:0000269|PubMed:21177872, ECO:0000269|PubMed:21251231}.;
Recessive Scores
- pRec
- 0.149
Intolerance Scores
- LoFtool
- 0.512
- RVIS EVS
- 0.26
- RVIS percentile EVS
- 70.06
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.987
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |