SMARCAD1

Chr 4AD

SNF2 related chromatin remodeling ATPase with DExD box 1

Also known as: ADERM, BASNS, ETL1, HEL1, HPGDS-AS1, HRZ, TYS

The SMARCAD1 protein is an ATP-dependent chromatin remodeling enzyme that facilitates DNA repair and maintains heterochromatin organization by mediating histone modifications and nucleosome assembly. Mutations cause autosomal dominant ectodermal disorders including adermatoglyphia (absence of fingerprints), Basan syndrome, and Huriez syndrome. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

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

AdermatoglyphiaMIM #136000
AD
Basan syndromeMIM #129200
AD
Huriez syndromeMIM #181600
AD
0
Active trials
6
Pubs (1 yr)
31
P/LP submissions
0%
P/LP missense
0.08
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummarySMARCAD1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 89 VUS of 180 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 6.90
OE 0.02 (0.010.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.49Z-score
OE missense 0.57 (0.520.63)
304 obs / 530.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.02 (0.010.08)
00.351.4
Missense OE0.57 (0.520.63)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 1 / 57.4Missense obs/exp: 304 / 530.3Syn Z: -0.64
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateSMARCAD1-related Huriez syndromeOTHERAD
DN
0.3495th %ile
GOF
0.2795th %ile
LOF
0.68top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 19% of P/LP variants are LoF · LOEUF 0.08

Literature Evidence

LOFSMARCAD1 Haploinsufficiency Underlies Huriez Syndrome and Associated Skin Cancer SusceptibilityPMID:29409814

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

180 submitted variants in ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic4
VUS89
Likely Benign11
Benign21
Conflicting1
23
Pathogenic
4
Likely Pathogenic
89
VUS
11
Likely Benign
21
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
19
0
23
Likely Pathogenic
1
0
3
0
4
VUS
0
84
5
0
89
Likely Benign
0
4
1
6
11
Benign
0
4
12
5
21
Conflicting
1
Total5924011149

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

View in ClinVar →

Protein Context — Lollipop Plot

SMARCAD1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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