APCDD1

Chr 18AD

APC down-regulated 1

Also known as: B7323, DRAPC1, FP7019, HHS, HTS, HYPT1

The protein functions as a negative regulator of the Wnt signaling pathway, inhibiting Wnt signaling upstream of beta-catenin through interactions with Wnt and LRP proteins. Mutations cause hypotrichosis 1, characterized by hereditary hair loss, and follow an autosomal dominant inheritance pattern. The gene shows low constraint to loss-of-function variants (pLI 0.007), suggesting tolerance to complete protein loss.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Hypotrichosis 1MIM #605389
AD
0
Active trials
9
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.68
LOEUF
DN
Mechanism· predicted
Clinical SummaryAPCDD1
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.007
Z-score 2.59
OE 0.36 (0.200.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.48Z-score
OE missense 0.92 (0.841.02)
291 obs / 315.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.200.68)
00.351.4
Missense OE0.92 (0.841.02)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 7 / 19.3Missense obs/exp: 291 / 315.1Syn Z: -0.95
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedAPCDD1-related generalised hereditary hypotrichosis simplex/hypotrichosisOTHERAD
DN
0.5378th %ile
GOF
0.4579th %ile
LOF
0.3647th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DN1 literature citation

Literature Evidence

DNAPCDD1(L9R) probably functions in a dominant-negative manner to inhibit the stability and membrane localization of the wild-type protein.PMID:20393562

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

APCDD1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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