GeneBe

SMARCAD1

protein-coding

SWI/SNF-related, matrix-associated actin-dependent regulator of chromatin, subfamily a, containing DEAD/H box 1

Gene summary

This gene encodes a member of the SNF subfamily of helicase proteins. The encoded protein plays a critical role in the restoration of heterochromatin organization and propagation of epigenetic patterns following DNA replication by mediating histone H3/H4 deacetylation. Mutations in this gene are associated with adermatoglyphia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

MANE transcript

NM_020159.5

Inheritance

AD

ClinVar variants

U:101B:29

Top phenotype

Huriez syndrome

gnomAD constraint

pLI —, LoF o/e 0.02

Max pathogenic AF

—

Genomic locus

chr4:94,207,611-94,291,292

External References & Databases

Ensembl (ENSG00000163104)NCBI Gene (56916)OMIM (612761)HGNC:18398GenCCUniProt (Q9H4L7)AlphaFoldClinVar (SMARCAD1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~83.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

absence of fingerprints-congenital milia syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007507

Submitter: Orphanet

palmoplantar keratoderma-sclerodactyly syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008416

Submitter: Orphanet

isolated congenital adermatoglyphiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007619

Submitter: Orphanet

isolated congenital adermatoglyphiaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007619

Submitter: Labcorp Genetics (formerly Invitae)

ectodermal dysplasia syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019287

Submitter: Illumina

palmoplantar keratoderma-sclerodactyly syndromeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0008416

Submitter: G2P

isolated congenital adermatoglyphiaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007619

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Huriez syndromeAD

Manifestation: Dermatologic; Oncologic

Intervention: Oncologic

Rationale: Huriez syndrome has been described as involving significant risk of aggressive squamous cell skin carcinoma, and awareness may allow surveillance and early management of disease

Refs: 4298032; 8731679; 10631162; 20619487; 21820097; 24664640; 24909267; 26932190; 29409814Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SMARCAD1 variants in ClinVar

8 Conditions Cataloged
Inborn genetic diseasesTotal: 88
not specifiedTotal: 22
not providedTotal: 19
SMARCAD1-related disorderTotal: 10
AdermatoglyphiaTotal: 4
Keratoderma with scleroatrophy of the extremitiesTotal: 3
Basan syndromeTotal: 3
Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020159.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
19
clinvar
1
clinvar
 20
missense
93
clinvar
7
clinvar
2
clinvar
 102
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
8
clinvar
 8
Total00101263130
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_020159.5RefSeqNP_064544.223MANE Select
ENST00000354268.9EnsemblENSP00000346217.423MANE Select
NM_001128429.3RefSeqNP_001121901.123Standard
NM_001128430.2RefSeqNP_001121902.123Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)

Biological Process

  • regulation of DNA recombination
  • DNA double-strand break processing
  • chromatin organization
  • chromatin remodeling
  • nucleotide metabolic process

Molecular Function

  • nucleic acid binding
  • DNA binding
  • helicase activity
  • protein binding
  • ATP binding

Cellular Component

  • heterochromatin
  • nucleoplasm
  • nuclear matrix
  • site of double-strand break
  • nuclear replication fork

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000359052
Coding exons
23
Length
83682
Individuals with no LoFs
125659
Homozygous LoFs
0
Heterozygous LoFs
2
Defined
125661
p
0.00000796
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.493045300.5730.00002596877
Missense (PolyPhen)34150.290.226231874
Synonymous-0.6431911801.060.000008821797
Loss of Function6.90157.40.01740.00000291717

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian0.0000580.000054rare
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: DNA helicase that possesses intrinsic ATP-dependent nucleosome-remodeling activity and is both required for DNA repair and heterochromatin organization. Promotes DNA end resection of double-strand breaks (DSBs) following DNA damage: probably acts by weakening histone DNA interactions in nucleosomes flanking DSBs. Required for the restoration of heterochromatin organization after replication. Acts at replication sites to facilitate the maintenance of heterochromatin by directing H3 and H4 histones deacetylation, H3 'Lys-9' trimethylation (H3K9me3) and restoration of silencing. {ECO:0000269|PubMed:21549307, ECO:0000269|PubMed:22960744}.;
Disease
DISEASE: Basan syndrome (BSNS) [MIM:129200]: An autosomal dominant form of adermatoglyphia associated with congenital facial milia, acral blistering, digital contractures, and nail abnormalities. Adermatoglyphia is defined by the lack of epidermal ridges on the palms and soles, which results in the absence of fingerprints. {ECO:0000269|PubMed:24664640, ECO:0000269|PubMed:26932190}. Note=The disease is caused by mutations affecting the gene represented in this entry. Splice site mutations causing aberrant splicing of skin-specific isoform 3 are likely to exert a loss-of- function effect and are involved in BSNS. {ECO:0000269|PubMed:24664640, ECO:0000269|PubMed:26932190}.;

Recessive Scores

pRec
0.247

Intolerance Scores

LoFtool
0.0130
RVIS EVS
0.27
RVIS percentile EVS
70.58

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.949

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium
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