FSIP2

protein-coding

fibrous sheath interacting protein 2

Gene summary

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]

MANE transcript

NM_173651.4

Inheritance

ClinVar variants

P:36U:933B:203

Top phenotype

Spermatogenic failure 34

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr2:185,738,804-185,833,290

External References & Databases

Ensembl (ENSG00000188738)

Transcript & Mutation Effects

hg38 • Region Span ~94.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

non-syndromic male infertility due to sperm motility disorderSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017173

Submitter: Orphanet

spermatogenic failure 34STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0029148

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spermatogenic failure 34AR

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: 30137358

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FSIP2 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 1012

FSIP2-related disorderTotal: 111

not providedTotal: 74

Spermatogenic failure 34Total: 44

Abnormal sperm morphologyTotal: 1

Long QT syndromeTotal: 1

Reduced sperm motilityTotal: 1

OligospermiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173651.4. 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	70 clinvar	7 clinvar	78
missense	4 clinvar	1 clinvar	929 clinvar	108 clinvar	18 clinvar	1060
nonsense	2 clinvar	4 clinvar				6
start loss						0
frameshift	7 clinvar	18 clinvar	2 clinvar			27
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	13	23	933	178	25	1172

Highest pathogenic variant AF is 0.0004725001

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173651.4	RefSeq	NP_775922.3	23	MANE Select
ENST00000424728.6	Ensembl	ENSP00000401306.1	23	MANE Select
ENST00000415915.5	Ensembl	ENSP00000390251.1	2	Standard
ENST00000429412.1	Ensembl	ENSP00000395888.1	5	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000343098
Coding exons: 23
Length: 94663
Individuals with no LoFs: 123370
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 123380
p: 0.0000405

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.31	2489	3.00e+3	0.830	0.000142	46142
Missense (PolyPhen)		574	746.05	0.76939		12660
Synonymous	3.77	930	1.09e+3	0.854	0.0000533	12966
Loss of Function	7.35	81	190	0.425	0.00000924	3457

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000032	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000061	0.000056	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000047	0.000045	rare
South Asian	0.000034	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0762

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.501

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High