HEPHL1

Chr 11

hephaestin like 1

Also known as: HJDD, ZP

NCBI Gene: 341208 ENSG00000181333 UniProt: Q6MZM0

Enables ferroxidase activity. Involved in intracellular iron ion homeostasis. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtAbnormal hair, joint laxity, and developmental delay

Clinical highlights

Gene–disease validity (ClinGen)

Limited · pili torti-developmental delay-neurological abnormalities syndrome · AR · ClinGen 2025

not for standalone diagnostic reporting

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.18

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.18LOEUF

pLI 0.000

Z-score 0.41

OE 0.94 (0.76–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.18Z-score

OE missense 0.98 (0.92–1.05)

622 obs / 635.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.94 (0.76–1.18)

0≤0.351.4

Missense OE?0.98 (0.92–1.05)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 54 / 57.3Missense obs/exp: 622 / 635.0Syn Z: -0.61

Background carrier burden — how many people carry a rare variant somewhere in HEPHL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 37

1,566 rare PASS variants

Rare truncating (LoF)

1 in 280

250 rare PASS variants

Rare synonymous (reference)

1 in 63

563 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HEPHL1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 46	1 in 310
South Asian	~43k	1 in 31	1 in 230
Remaining (unassigned)	~30k	1 in 31	1 in 230
European (Finnish)	~27k	1 in 130	1 in 3,800
Admixed American	~22k	1 in 33	1 in 290
African / African American	~21k	1 in 33	1 in 240
East Asian	~20k	1 in 35	1 in 250
Ashkenazi Jewish	~13k	1 in 220	1 in 1,500
Middle Eastern	~2,884	1 in 31	1 in 240

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 18 of 20 coding exons well covered in gnomAD exomes; exons 15, 17 marginal. Genomes: all 20.? see exons ↓