HIF1AN

hypoxia inducible factor 1 subunit alpha inhibitor, the group of JmjC hydroxylases

Basic information

Region (hg38): 10:100529072-100559998

Links

ENSG00000166135 ∙ NCBI:55662 ∙ OMIM:606615 ∙ HGNC:17113 ∙ Uniprot:Q9NWT6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HIF1AN gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HIF1AN gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			6			6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	6	0	0

Variants in HIF1AN

This is a list of pathogenic ClinVar variants found in the HIF1AN region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-100529321-C-A			Benign (May 13, 2021)
10-100529360-G-A			Likely benign (Jan 16, 2022)
10-100529372-T-C		NDUFB8-related disorder	Likely benign (Aug 04, 2023)
10-100529377-C-T		NDUFB8-related disorder	Likely benign (Jun 25, 2020)
10-100529393-C-T		Inborn genetic diseases	Likely benign (Jan 28, 2024)
10-100529402-GT-G		Mitochondrial complex 1 deficiency, nuclear type 32	Uncertain significance (Sep 27, 2023)
10-100529408-A-G		Mitochondrial complex 1 deficiency, nuclear type 32	Pathogenic (Dec 13, 2018)
10-100529423-T-G		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
10-100529434-T-C			Uncertain significance (May 09, 2022)
10-100529445-G-A			Likely benign (Jul 05, 2022)
10-100529466-A-G			Likely benign (May 01, 2024)
10-100529485-A-G		Inborn genetic diseases	Uncertain significance (Mar 31, 2024)
10-100529487-G-A			Likely benign (Apr 24, 2022)
10-100529505-G-C			Likely benign (Aug 22, 2022)
10-100529509-A-G			Uncertain significance (Aug 22, 2022)
10-100529510-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jun 29, 2022)
10-100529517-G-A			Likely benign (Jun 29, 2023)
10-100529522-G-T			Likely benign (Jul 25, 2023)
10-100529731-C-T			Benign (May 18, 2021)
10-100529761-G-A			Uncertain significance (Aug 27, 2022)
10-100529767-C-G			Uncertain significance (Jun 29, 2023)
10-100529774-T-C			Likely benign (Jul 25, 2022)
10-100529804-C-G			Uncertain significance (Dec 02, 2021)
10-100529817-T-C		Inborn genetic diseases	Likely benign (Nov 29, 2023)
10-100529819-G-T		NDUFB8-related disorder	Likely benign (Jan 12, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HIF1AN	protein_coding	protein_coding	ENST00000299163	8	30927

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0739	0.926	125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.02	111	189	0.587	0.00000912	2315
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000960	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000442	0.0000439
Middle Eastern	0.0000544	0.0000544
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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;Cellular response to hypoxia;Cellular responses to stress;HIF-2-alpha transcription factor network;Hypoxic and oxygen homeostasis regulation of HIF-1-alpha;Cellular responses to external stimuli (Consensus)

Recessive Scores

• pRec: 0.149

Intolerance Scores

• loftool: 0.512
• rvis_EVS: 0.26
• rvis_percentile_EVS: 70.06

Haploinsufficiency Scores

• pHI: 0.540
• hipred: Y
• hipred_score: 0.783
• ghis: 0.513

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.987

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hif1an
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: hif1an
• Affected structure: angiogenic sprout
• Phenotype tag: abnormal
• Phenotype quality: mislocalised

Gene ontology

• Biological process: peptidyl-histidine hydroxylation;peptidyl-aspartic acid hydroxylation;peptidyl-asparagine hydroxylation;positive regulation of myoblast differentiation;negative regulation of Notch signaling pathway;oxidation-reduction process;regulation of transcription from RNA polymerase II promoter in response to hypoxia;negative regulation of transcription from RNA polymerase II promoter in response to hypoxia;positive regulation of vasculogenesis
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;perinuclear region of cytoplasm
• Molecular function: Notch binding;iron ion binding;protein binding;zinc ion binding;2-oxoglutarate-dependent dioxygenase activity;oxygen sensor activity;carboxylic acid binding;peptidyl-histidine dioxygenase activity;peptidyl-asparagine 3-dioxygenase activity;protein homodimerization activity;cofactor binding;NF-kappaB binding;ankyrin repeat binding;hypoxia-inducible factor-asparagine oxygenase activity