HEPHL1

hephaestin like 1

Basic information

Region (hg38): 11:94021353-94114208

Links

ENSG00000181333 ∙ NCBI:341208 ∙ OMIM:618455 ∙ HGNC:30477 ∙ Uniprot:Q6MZM0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pili torti-developmental delay-neurological abnormalities syndrome (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Abnormal hair, joint laxity, and developmental delay	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Dermatologic; Musculoskeletal; Neurologic	31125343

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HEPHL1 gene.

• Inborn genetic diseases (48 variants)
• not provided (15 variants)
• Pili torti-developmental delay-neurological abnormalities syndrome (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HEPHL1 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				6		6
missense			50	3	1	54
nonsense		3	1			4
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding					2	2
Total	0	3	52	9	3

Highest pathogenic variant AF is 0.000197

Variants in HEPHL1

This is a list of pathogenic ClinVar variants found in the HEPHL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-94021375-C-T		not specified	Uncertain significance (Nov 10, 2021)
11-94021412-T-C		not specified	Uncertain significance (Jan 31, 2024)
11-94021468-G-T		not specified	Uncertain significance (Apr 19, 2023)
11-94021492-C-T		not specified	Uncertain significance (Sep 25, 2023)
11-94045706-C-G		not specified	Uncertain significance (Aug 16, 2021)
11-94045717-G-A		not specified	Uncertain significance (Feb 21, 2024)
11-94045721-T-G		not specified	Uncertain significance (Feb 07, 2023)
11-94045730-G-T		not specified	Uncertain significance (May 09, 2023)
11-94045743-C-T		HEPHL1-related disorder	Likely benign (Nov 16, 2019)
11-94045759-C-T		not specified	Uncertain significance (Oct 18, 2021)
11-94045787-C-G			Likely benign (Mar 01, 2023)
11-94045789-G-C		not specified	Uncertain significance (Dec 21, 2022)
11-94045866-C-T			Likely pathogenic (Apr 28, 2021)
11-94045893-G-A			Uncertain significance (Nov 01, 2023)
11-94063535-G-C		not specified	Uncertain significance (Feb 13, 2024)
11-94063610-C-A		not specified	Uncertain significance (Feb 23, 2023)
11-94063616-C-T		HEPHL1-related disorder	Likely benign (Nov 26, 2019)
11-94063665-C-T			Likely benign (Nov 01, 2022)
11-94064339-A-AATAG		Pili torti-developmental delay-neurological abnormalities syndrome	Likely pathogenic (-)
11-94064373-G-A		HEPHL1-related disorder	Benign (Dec 05, 2019)
11-94064415-G-C		not specified	Uncertain significance (Dec 16, 2023)
11-94064417-T-C		not specified	Uncertain significance (Mar 22, 2023)
11-94064453-A-G		Pili torti-developmental delay-neurological abnormalities syndrome • HEPHL1-related disorder	Benign (Aug 10, 2021)
11-94067538-T-C			Uncertain significance (Jul 01, 2023)
11-94067539-G-A		not specified	Uncertain significance (Nov 02, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HEPHL1	protein_coding	protein_coding	ENST00000315765	20	92391

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.15e-34	0.0000470	124272	1	378	124651	0.00152

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.184	622	635	0.979	0.0000326	7663
Missense in Polyphen		247	255.14	0.96809		3158
Synonymous	-0.606	248	236	1.05	0.0000131	2180
Loss of Function	0.409	54	57.3	0.942	0.00000334	646

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00267	0.00267
Ashkenazi Jewish	0.00	0.00
East Asian	0.00434	0.00429
Finnish	0.000975	0.000975
European (Non-Finnish)	0.00121	0.00120
Middle Eastern	0.00434	0.00429
South Asian	0.00212	0.00206
Other	0.00252	0.00248

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May function as a ferroxidase and may be involved in copper transport and homeostasis. {ECO:0000250}.
• Pathway: Iron metabolism in placenta (Consensus)

Intolerance Scores

• loftool: 0.207
• rvis_EVS: -0.28
• rvis_percentile_EVS: 33.59

Haploinsufficiency Scores

• pHI: 0.283
• hipred: N
• hipred_score: 0.197
• ghis: 0.405

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.269

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hephl1

Gene ontology

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