SSX1

protein-coding

SSX family member 1, the group of SSX family

Gene summary

The product of this gene belongs to the family of highly homologous synovial sarcoma X (SSX) breakpoint proteins. These proteins may function as transcriptional repressors. They are also capable of eliciting spontaneous humoral and cellular immune responses in cancer patients, and are potentially useful targets in cancer vaccine-based immunotherapy. This gene, and also the SSX2 and SSX4 family members, have been involved in t(X;18)(p11.2;q11.2) translocations that are characteristically found in all synovial sarcomas. This translocation results in the fusion of the synovial sarcoma translocation gene on chromosome 18 to one of the SSX genes on chromosome X. The encoded hybrid proteins are likely responsible for transforming activity. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome X. [provided by RefSeq, Jul 2013]

MANE transcript

NM_005635.4

Inheritance

ClinVar variants

P:3U:61B:9

Top phenotype

Spermatogenic failure, X-linked, 5

gnomAD constraint

pLI —, LoF o/e 6.5

Max pathogenic AF

—

Genomic locus

chrX:48,255,392-48,267,444

External References & Databases

Ensembl (ENSG00000126752)

Transcript & Mutation Effects

hg38 • Region Span ~12.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure, X-linked, 5STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0859477

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spermatogenic failure, X-linked, 5XL

Manifestation: Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 36796361

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SSX1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 49

not providedTotal: 7

SSX1-related disorderTotal: 6

Spermatogenic failure, X-linked, 5Total: 3

TeratomaTotal: 1

Synovial sarcomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005635.4. 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	1 clinvar		2
missense	1 clinvar		52 clinvar	7 clinvar		60
nonsense			1 clinvar	1 clinvar		2
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)	1 clinvar		6 clinvar			7
Total	3	0	61	9	0	73

Highest pathogenic variant AF is 0.000036143567

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005635.4	RefSeq	NP_005626.1	6	MANE Select
ENST00000376919.4	Ensembl	ENSP00000366118.3	6	MANE Select
NM_001278691.2	RefSeq	NP_001265620.1	6	Standard
ENST00001093008.1	Ensembl	ENSP00000762814.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Transcriptional misregulation in cancer - Homo sapiens (human)

Biological Process

regulation of transcription, DNA-templated
negative regulation of nucleic acid-templated transcription

Molecular Function

nucleic acid binding
transcription corepressor activity
protein binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376919
Coding exons: 6
Length: 12128
Individuals with no LoFs: 125650
Homozygous LoFs: 36
Heterozygous LoFs: 56
Defined: 125742
p: 0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-4.37	176	71.7	2.45	0.00000533	1264
Missense (PolyPhen)		40	12.829	3.118		280
Synonymous	-0.567	32	28.2	1.14	0.00000246	301
Loss of Function	-13.4	45	6.92	6.50	4.36e-7	139

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00039	0.00031	rare
Latino/Admixed American	0.00088	0.00064	rare
Ashkenazi Jewish	0.00013	0.000099	rare
East Asian	0.00065	0.00049	rare
Finnish	0.00013	0.000092	rare
European (Non-Finnish)	0.00041	0.00029	rare
South Asian	0.0011	0.00062	notable
Other	0.00022	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Could act as a modulator of transcription.;

Intolerance Scores

LoFtool: 0.871
RVIS EVS: 0.28
RVIS percentile EVS: 71.41

Essentials

Essential (CRISPR): 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