HIF3A

hypoxia inducible factor 3 subunit alpha, the group of Basic helix-loop-helix proteins|PAS domain containing

Basic information

Region (hg38): 19:46297041-46343433

Links

ENSG00000124440 ∙ NCBI:64344 ∙ OMIM:609976 ∙ HGNC:15825 ∙ Uniprot:Q9Y2N7 ∙ 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 HIF3A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HIF3A 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				1		1
missense			48	6	1	55
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	2	3
non coding						0
Total	0	0	48	7	1

Variants in HIF3A

This is a list of pathogenic ClinVar variants found in the HIF3A region.

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

Position	Type	Phenotype	Significance	ClinVar
19-46297093-A-G		not specified	Uncertain significance (May 30, 2024)
19-46303900-C-G		not specified	Uncertain significance (Dec 16, 2023)
19-46303949-G-A		not specified	Likely benign (Nov 21, 2023)
19-46304040-A-G		not specified	Uncertain significance (Mar 25, 2024)
19-46304057-C-T		not specified	Likely benign (Mar 20, 2024)
19-46304073-C-T		not specified	Uncertain significance (Nov 30, 2021)
19-46304074-G-A		not specified	Uncertain significance (Oct 06, 2022)
19-46305262-G-A		not specified	Uncertain significance (Jun 30, 2022)
19-46305334-G-A		not specified	Uncertain significance (Oct 03, 2022)
19-46305359-A-G		not specified	Uncertain significance (Jul 19, 2023)
19-46308231-T-C		not specified	Uncertain significance (Mar 23, 2022)
19-46308299-C-G		not specified	Uncertain significance (Oct 26, 2022)
19-46308302-C-A		not specified	Uncertain significance (Dec 20, 2021)
19-46308683-G-A		not specified	Uncertain significance (Sep 20, 2023)
19-46308697-G-T		not specified	Uncertain significance (Feb 27, 2024)
19-46308714-G-A		not specified	Uncertain significance (Jan 09, 2024)
19-46308740-G-A		not specified	Uncertain significance (Jan 30, 2024)
19-46308744-G-A		not specified	Uncertain significance (Feb 05, 2024)
19-46308755-C-G		not specified	Uncertain significance (Aug 30, 2021)
19-46309153-G-A			Likely benign (Mar 30, 2018)
19-46309205-C-T		not specified	Uncertain significance (Dec 12, 2022)
19-46309268-C-A			Uncertain significance (Apr 25, 2023)
19-46309275-C-G		not specified	Uncertain significance (Nov 30, 2022)
19-46309292-C-T		not specified	Uncertain significance (Feb 22, 2023)
19-46309302-G-A		not specified	Uncertain significance (Dec 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HIF3A	protein_coding	protein_coding	ENST00000377670	15	46388

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00154	0.998	125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.757	370	413	0.895	0.0000255	4252
Missense in Polyphen		126	179.1	0.70352		1798
Synonymous	-0.200	182	179	1.02	0.0000116	1427
Loss of Function	3.19	10	28.3	0.353	0.00000129	333

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000345	0.000345
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000144	0.000141
Middle Eastern	0.000218	0.000217
South Asian	0.000133	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a transcriptional regulator in adaptive response to low oxygen tension. Acts as a regulator of hypoxia-inducible gene expression (PubMed:11573933, PubMed:16126907, PubMed:19694616, PubMed:20416395, PubMed:21069422). Functions as an inhibitor of angiogenesis in hypoxic cells of the cornea. Plays a role in the development of the cardiorespiratory system. May also be involved in apoptosis (By similarity). {ECO:0000250|UniProtKB:Q0VBL6, ECO:0000269|PubMed:11573933, ECO:0000269|PubMed:16126907, ECO:0000269|PubMed:19694616, ECO:0000269|PubMed:20416395, ECO:0000269|PubMed:21069422}.; FUNCTION: Isoform 3: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation. {ECO:0000269|PubMed:19694616, ECO:0000269|PubMed:20416395, ECO:0000269|PubMed:21069422}.; FUNCTION: Isoform 5: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation. {ECO:0000269|PubMed:21069422}.
• Pathway: Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha;Regulation of gene expression by Hypoxia-inducible Factor;Regulation of Hypoxia-inducible Factor (HIF) by oxygen;Cellular response to hypoxia;Cellular responses to stress;Post-translational protein modification;Metabolism of proteins;Hypoxic and oxygen homeostasis regulation of HIF-1-alpha;Cellular responses to external stimuli;Neddylation (Consensus)

Recessive Scores

• pRec: 0.154

Intolerance Scores

• loftool: 0.849
• rvis_EVS: -0.33
• rvis_percentile_EVS: 30.9

Haploinsufficiency Scores

• pHI: 0.918
• hipred: Y
• hipred_score: 0.701
• ghis: 0.525

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.864

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hif3a
• Phenotype: muscle 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); respiratory system phenotype

Gene ontology

• Biological process: angiogenesis;regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;apoptotic process;post-translational protein modification;positive regulation of transcription by RNA polymerase II;regulation of transcription from RNA polymerase II promoter in response to hypoxia
• Cellular component: nucleus;nucleoplasm;mitochondrion;cytosol;plasma membrane;nuclear speck
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;protein dimerization activity