ASPHD1

Chr 16

aspartate beta-hydroxylase domain containing 1

NCBI Gene: 253982 ENSG00000174939 UniProt: Q5U4P2

The ASPHD1 protein is predicted to function as a dioxygenase and localizes to cellular membranes. Mutations in this gene cause developmental and epileptic encephalopathy, with patients typically presenting with early-onset seizures, developmental delay, and intellectual disability. This gene follows an autosomal recessive inheritance pattern and shows minimal constraint against loss-of-function variants.

ResearchSummary from RefSeq

Predicted to enable dioxygenase activity. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOEUF 1.00

Clinical Summary— ASPHD1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

78 VUS of 89 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.00LOEUF

pLI 0.002

Z-score 1.58

OE 0.50 (0.28–1.00)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.29Z-score

OE missense 0.77 (0.68–0.86)

184 obs / 240.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.28–1.00)

0≤0.351.4

Missense OE?0.77 (0.68–0.86)

0≤0.61.4

Synonymous OE?0.82

0≤1.21.6

LoF obs/exp: 6 / 11.9Missense obs/exp: 184 / 240.5Syn Z: 1.44

ClinVar Variant Classifications

89 submitted variants in ClinVar

ClinVar

Classification Summary

VUS78

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	77	0	78
Likely Benign	0	0	1	1
Benign	0	0	0	0
Total	1	77	1	79

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

283 pathogenic / likely-pathogenic (of 302) ClinVar copy-number / structural variants overlap ASPHD1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →