TSSK1B

Chr 5

testis specific serine kinase 1B

Also known as: FKSG81, SPOGA4, STK22D, TSK1, TSSK1

NCBI Gene: 83942 ENSG00000212122 UniProt: Q9BXA7

TSSK1 belongs to a family of serine/threonine kinases highly expressed in testis (Hao et al., 2004 [PubMed 15044604]).[supplied by OMIM, Mar 2008]

Research

TSSK1 belongs to a family of serine/threonine kinases highly expressed in testis (Hao et al., 2004 [PubMed 15044604]).[supplied by OMIM, Mar 2008]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.71

Clinical Summary— TSSK1B

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

70 VUS of 72 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.71LOEUF

pLI 0.000

Z-score 0.17

OE 0.93 (0.50–1.71)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.34Z-score

OE missense 1.06 (0.96–1.18)

260 obs / 244.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.93 (0.50–1.71)

0≤0.351.4

Missense OE?1.06 (0.96–1.18)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 6 / 6.5Missense obs/exp: 260 / 244.9Syn Z: -0.70

This gene — mechanism propensity

0.6939th %ile

GOF

0.76top 25%

LOF

0.2968th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

72 submitted variants in ClinVar

ClinVar

Classification Summary

VUS70

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	70	0	70
Likely Benign	1	1	2
Benign	0	0	0
Total	71	1	72

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap TSSK1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →