TWSG1

protein-coding

twisted gastrulation BMP signaling modulator 1

Gene summary

Enables transforming growth factor beta binding activity. Involved in negative regulation of CD4-positive, alpha-beta T cell proliferation; negative regulation of cytokine production; and positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway. Located in centrosome and cytosol. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_020648.6

Inheritance

—

ClinVar variants

U:28B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr18:9,334,767-9,402,420

External References & Databases

Ensembl (ENSG00000128791)

Transcript & Mutation Effects

hg38 • Region Span ~67.7 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 TWSG1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 24

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020648.6. 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			1 clinvar	2 clinvar		3
missense			24 clinvar			24
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	28	2	0	30

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020648.6	RefSeq	NP_065699.1	4	MANE Select
ENST00000262120.10	Ensembl	ENSP00000262120.5	4	MANE Select
ENST00000581641.1	Ensembl	ENSP00000464458.1	3	Standard
ENST00000581641.2	Ensembl	ENSP00000464458.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
twsg1b	Danio rerio	Structure: dorsal longitudinal anastomotic vessel Quality: malformed abnormal

Gene / Model

Organism

Observed Phenotype

twsg1b

Danio rerio

Structure: dorsal longitudinal anastomotic vessel

Quality: malformed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mesodermal Commitment Pathway

Biological Process

ossification
mesoderm formation
negative regulation of cytokine production
transforming growth factor beta receptor signaling pathway
salivary gland morphogenesis

Molecular Function

protein binding
transforming growth factor beta binding

Cellular Component

extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262120
Coding exons: 4
Length: 67654
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125748
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.951	97	127	0.763	0.00000644	1490
Missense (PolyPhen)		32	39.696	0.80613		459
Synonymous	0.0150	44	44.1	0.997	0.00000240	395
Loss of Function	1.51	5	10.2	0.490	4.95e-7	123

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00041	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0.00029	0.00028	rare
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in dorsoventral axis formation. Seems to antagonize BMP signaling by forming ternary complexes with CHRD and BMPs, thereby preventing BMPs from binding to their receptors. In addition to the anti-BMP function, also has pro-BMP activity, partly mediated by cleavage and degradation of CHRD, which releases BMPs from ternary complexes. May be an important modulator of BMP-regulated cartilage development and chondrocyte differentiation. May play a role in thymocyte development (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.309

Intolerance Scores

RVIS EVS: -0.14
RVIS percentile EVS: 43.29

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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