FSIP2

Chr 2AR

fibrous sheath interacting protein 2

Also known as: SPGF34

NCBI Gene: 401024 ENSG00000188738 UniProt: Q5CZC0 OMIM: 615796

The protein is a structural component of the sperm fibrous sheath that is specifically expressed in spermatogenic cells during the postmeiotic phase of spermatogenesis. Mutations cause spermatogenic failure 34, an autosomal recessive condition leading to male infertility. This gene is highly constrained against loss-of-function variants, indicating its critical role in normal sperm development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein associated with the sperm fibrous sheath. Genes encoding most of the fibrous-sheath associated proteins genes are transcribed only during the postmeiotic period of spermatogenesis. The protein encoded by this gene is specific to spermatogenic cells. Copy number variation in this gene may be associated with testicular germ cell tumors. Pseudogenes associated with this gene are reported on chromosomes 2 and X. [provided by RefSeq, Aug 2016]

OMIM ResearchGenerating clinical summary…

GOFmechanismARLOEUF 0.511 OMIM phenotype

Clinical Summary— FSIP2

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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

24 unique Pathogenic / Likely Pathogenic· 941 VUS of 1209 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

0.51LOEUF

pLI 0.000

Z-score 7.35

OE 0.43 (0.35–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

3.31Z-score

OE missense 0.83 (0.80–0.86)

2489 obs / 2998.7 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.43 (0.35–0.51)

0≤0.351.4

Missense OE?0.83 (0.80–0.86)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 81 / 190.4Missense obs/exp: 2489 / 2998.7Syn Z: 3.77

This gene — mechanism propensity

0.5869th %ile

GOF

0.94top 5%

LOF

0.2484th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

1209 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14

Likely Pathogenic10

VUS941

Likely Benign159

Benign63

Conflicting10

Pathogenic

Likely Pathogenic

941

VUS

159

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	9	5	0	0	14
Likely Pathogenic	9	1	0	0	10
VUS	2	918	21	0	941
Likely Benign	0	100	5	54	159
Benign	0	44	0	19	63
Conflicting	—				10
Total	20	1,068	26	73	1,197

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 38) ClinVar copy-number / structural variants overlap FSIP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →