HID1

Chr 17AR

HID1 domain containing

Also known as: 17orf28, C17orf28, DEE105, DMC1, HID-1

NCBI Gene: 283987 ENSG00000167861 UniProt: Q8IV36 OMIM: 605752

The protein is predicted to function in insulin processing, secretory granule maturation, and vesicle trafficking within the Golgi apparatus and cytosol. Mutations cause developmental and epileptic encephalopathy 105, which typically presents in early childhood with seizures and developmental delays. This gene shows significant constraint against loss-of-function variants (LOEUF 0.47), suggesting that complete loss of protein function is likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to act upstream of or within several processes, including insulin processing; secretory granule maturation; and vacuole fusion, non-autophagic. Located in Golgi apparatus; cytoplasmic microtubule; and cytosol. Implicated in developmental and epileptic encephalopathy 105. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 105 with hypopituitarismMIM #619983

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Developmental and epileptic encephalopathy 105 with hypopituitarism; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.47

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.027

Z-score 4.02

OE 0.28 (0.17–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.27Z-score

OE missense 0.70 (0.64–0.77)

325 obs / 462.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.28 (0.17–0.47)

0≤0.351.4

Missense OE?0.70 (0.64–0.77)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 10 / 36.0Missense obs/exp: 325 / 462.0Syn Z: 0.63

Background carrier burden — how many people carry a rare variant somewhere in HID1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 57

974 rare PASS variants

Rare truncating (LoF)

1 in 2,000

112 rare PASS variants

Rare synonymous (reference)

1 in 64

510 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HID1. 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 70	1 in 1,600
South Asian	~43k	1 in 49	1 in 3,100
Remaining (unassigned)	~30k	1 in 47	1 in 690
European (Finnish)	~27k	1 in 110	1 in 490
Admixed American	~22k	1 in 58	1 in 860
African / African American	~21k	1 in 46	1 in 3,000
East Asian	~20k	1 in 60	1 in 640
Ashkenazi Jewish	~13k	1 in 270	1 in 420
Middle Eastern	~2,884	1 in 78	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 18 of 19 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: 18 of 19 (exon 10 below).? see exons ↓