FLYWCH1

protein-coding

FLYWCH-type zinc finger 1, the group of Zinc fingers

Gene summary

Enables transcription coactivator binding activity and transcription corepressor activity. Involved in DNA damage response and negative regulation of transcription by RNA polymerase II. Located in nuclear body and pericentric heterochromatin. Part of transcription regulator complex. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001308068.2

Inheritance

—

ClinVar variants

U:226B:23

Top phenotype

Russell-Silver syndrome

gnomAD constraint

pLI —, LoF o/e 0.98

Max pathogenic AF

—

Genomic locus

chr16:2,911,931-2,951,208

External References & Databases

Ensembl (ENSG00000059122)

Transcript & Mutation Effects

hg38 • Region Span ~39.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FLYWCH1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 219

not providedTotal: 14

Russell-Silver syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001308068.2. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	6 clinvar	2 clinvar	14
missense			214 clinvar	13 clinvar	2 clinvar	229
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	226	19	4	249

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 105 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001308068.2	RefSeq	NP_001294997.1	8	MANE Select
ENST00000253928.14	Ensembl	ENSP00000253928.9	8	MANE Select
NM_020912.2	RefSeq	NP_065963.1	7	Standard
NM_032296.3	RefSeq	NP_115672.2	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

DNA binding
metal ion binding

Cellular Component

nucleoplasm
cytosol
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000416288
Coding exons: 8
Length: 39272
Individuals with no LoFs: 125303
Homozygous LoFs: 0
Heterozygous LoFs: 247
Defined: 125550
p: 0.000984

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.61	606	450	1.35	0.0000322	4451
Missense (PolyPhen)		172	126.78	1.3567		1191
Synonymous	-5.20	284	192	1.48	0.0000130	1484
Loss of Function	0.0761	28	28.4	0.985	0.00000169	293

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00073	0.00062	rare
Latino/Admixed American	0.00033	0.00032	rare
Ashkenazi Jewish	0.014	0.014	notable
East Asian	0.00083	0.00071	rare
Finnish	0.00051	0.00051	rare
European (Non-Finnish)	0.00033	0.00031	rare
South Asian	0.00054	0.00052	rare
Other	0.0025	0.0025	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.159
RVIS EVS: -0.37
RVIS percentile EVS: 28.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.869

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium