HEPH

hephaestin

Basic information

Region (hg38): X:66162671-66268867

Links

ENSG00000089472 ∙ NCBI:9843 ∙ OMIM:300167 ∙ HGNC:4866 ∙ Uniprot:Q9BQS7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary hemochromatosis (Moderate), mode of inheritance: XL

ClinVar

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

• not_specified (122 variants)
• not_provided (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HEPH gene is commonly pathogenic or not. These statistics are base on transcript: NM_001367233.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			116	8	1	125
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	116	9	1

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HEPH	protein_coding	protein_coding	ENST00000519389	21	106319

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000461	1.00	125713	10	21	125744	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.715	485	443	1.10	0.0000327	8011
Missense in Polyphen		149	171.04	0.87115		3154
Synonymous	-1.96	188	157	1.20	0.0000109	2314
Loss of Function	3.76	15	41.0	0.366	0.00000327	654

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000307	0.000260
Ashkenazi Jewish	0.00	0.00
East Asian	0.000297	0.000217
Finnish	0.000377	0.000277
European (Non-Finnish)	0.000164	0.000114
Middle Eastern	0.000297	0.000217
South Asian	0.000105	0.0000653
Other	0.000226	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May function as a ferroxidase for ferrous (II) to ferric ion (III) conversion and may be involved in copper transport and homeostasis. Implicated in iron homeostasis and may mediate iron efflux associated to ferroportin 1.
• Pathway: Porphyrin and chlorophyll metabolism - Homo sapiens (human);Mineral absorption - Homo sapiens (human);Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Metal ion SLC transporters;Iron uptake and transport (Consensus)

Recessive Scores

• pRec: 0.375

Intolerance Scores

• loftool: 0.0196
• rvis_EVS: 0.38
• rvis_percentile_EVS: 75.65

Haploinsufficiency Scores

• pHI: 0.221
• hipred: N
• hipred_score: 0.466
• ghis: 0.481

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.388

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Heph
• Phenotype: liver/biliary system phenotype; embryo phenotype; pigmentation phenotype; normal 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); hematopoietic system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; homeostasis/metabolism phenotype; immune system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: copper ion transport;iron ion transport;cellular iron ion homeostasis;iron ion homeostasis;oxidation-reduction process
• Cellular component: plasma membrane;integral component of membrane;basolateral plasma membrane;perinuclear region of cytoplasm
• Molecular function: ferroxidase activity;copper ion binding;ferrous iron binding;oxidoreductase activity