Spermatogenic failure 7

Summary

Spermatogenic failure 7 (MONDO:0013070) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 82

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spermatogenic failure 7
Mondo ID	MONDO:0013070
MeSH	C567832
OMIM	612997
DOID	DOID:0070173
UMLS	C2751811
MedGen	414478
GARD	0018400
Is cancer (heuristic)	no

Also known as: spermatogenic failure 7 · spermatogenic failure type 7 · SPGF7

Data availability: 82 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › spermatogenic failure › spermatogenic failure 7

Related subtypes (112): spermatogenic failure 6, spermatogenic failure 2, spermatogenic failure 5, spermatogenic failure 1, spermatogenic failure 4, spermatogenic failure, X-linked, 2, spermatogenic failure, Y-linked, 1, spermatogenic failure, Y-linked, 2, spermatogenic failure 3, spermatogenic failure 8, spermatogenic failure 9, spermatogenic failure 10, spermatogenic failure 11, spermatogenic failure 12, spermatogenic failure 13, spermatogenic failure 14, spermatogenic failure 15, spermatogenic failure 16, spermatogenic failure 17, spermatogenic failure 30, spermatogenic failure 31, spermatogenic failure 32, spermatogenic failure 54, spermatogenic failure, X-linked, 4, spermatogenic failure, X-linked, 3, spermatogenic failure 33, spermatogenic failure 34, spermatogenic failure 55, spermatogenic failure 56, spermatogenic failure 57, spermatogenic failure 58, spermatogenic failure 59, spermatogenic failure 60, spermatogenic failure 61, spermatogenic failure 62, spermatogenic failure 63, spermatogenic failure 64, spermatogenic failure 65, spermatogenic failure 66, spermatogenic failure 67, spermatogenic failure 68, spermatogenic failure 69, spermatogenic failure 70, spermatogenic failure 71, spermatogenic failure 72, spermatogenic failure 73, spermatogenic failure 47, spermatogenic failure 48, spermatogenic failure 49, spermatogenic failure 50, spermatogenic failure 51, spermatogenic failure 52, spermatogenic failure 74, spermatogenic failure 75, spermatogenic failure 53, spermatogenic failure 76, spermatogenic failure 77, spermatogenic failure 35, spermatogenic failure 36, spermatogenic failure 37, spermatogenic failure 38, spermatogenic failure 39, spermatogenic failure 40, spermatogenic failure 41, spermatogenic failure 42, spermatogenic failure 43, spermatogenic failure 44, spermatogenic failure 45, spermatogenic failure 46, spermatogenic failure 18, spermatogenic failure 19, spermatogenic failure 20, spermatogenic failure 21, spermatogenic failure 22, spermatogenic failure 23, spermatogenic failure 24, spermatogenic failure 25, spermatogenic failure 26, spermatogenic failure 27, spermatogenic failure 28, spermatogenic failure 29, X-linked spermatogenic failure 1, spermatogenic failure 98, spermatogenic failure 78, spermatogenic failure 79, spermatogenic failure 80, spermatogenic failure, X-linked, 5, spermatogenic failure, X-linked, 6, spermatogenic failure 81, spermatogenic failure, X-linked, 7, spermatogenic failure 82, spermatogenic failure 83, spermatogenic failure 84, spermatogenic failure 85, spermatogenic failure 86, spermatogenic failure 87, spermatogenic failure 88, spermatogenic failure 89, spermatogenic failure 90, spermatogenic failure, X-linked, 8, spermatogenic failure 91, spermatogenic failure 92, spermatogenic failure 93, spermatogenic failure 94, spermatogenic failure 95, spermatogenic failure 96, spermatogenic failure 97, spermatogenic failure, X-linked, 9, spermatogenic failure 99, spermatogenic failure 100, spermatogenic failure 101, spermatogenic failure 102

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

82 retrieved; paginated sample, class counts are floors:

53 uncertain significance, 10 conflicting classifications of pathogenicity, 7 benign, 5 benign/likely benign, 3 pathogenic, 2 likely benign, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4400	NM_053054.4(CATSPER1):c.539dup (p.His182fs)	CATSPER1	Pathogenic	no assertion criteria provided
4401	NM_053054.4(CATSPER1):c.944_948dup (p.Asp317fs)	CATSPER1	Pathogenic	no assertion criteria provided
165315	NM_153700.2(STRC):c.3670C>T (p.Arg1224Ter)	STRC	Pathogenic	criteria provided, multiple submitters, no conflicts
505435	NM_153700.2(STRC):c.4219-1G>A	STRC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2627058	NM_053054.4(CATSPER1):c.889C>T (p.Arg297Ter)	CATSPER1	Likely pathogenic	no assertion criteria provided
305424	NM_053054.4(CATSPER1):c.1544-6C>T	CATSPER1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305444	NM_053054.4(CATSPER1):c.688C>T (p.Arg230Cys)	CATSPER1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305448	NM_053054.4(CATSPER1):c.333C>T (p.Tyr111=)	CATSPER1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305450	NM_053054.4(CATSPER1):c.144C>T (p.His48=)	CATSPER1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
711064	NM_053054.4(CATSPER1):c.996G>C (p.Arg332=)	CATSPER1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
877902	NM_053054.4(CATSPER1):c.148G>A (p.Val50Met)	CATSPER1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
879482	NM_053054.4(CATSPER1):c.773G>A (p.Arg258His)	CATSPER1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
879841	NM_053054.4(CATSPER1):c.689G>A (p.Arg230His)	CATSPER1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
165311	NM_153700.2(STRC):c.4171C>G (p.Arg1391Gly)	STRC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3075838	NM_153700.2(STRC):c.4765G>A (p.Val1589Ile)	STRC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305414	NM_053054.4(CATSPER1):c.*96G>A	CATSPER1	Uncertain significance	criteria provided, single submitter
305415	NM_053054.4(CATSPER1):c.*23G>A	CATSPER1	Uncertain significance	criteria provided, single submitter
305416	NM_053054.4(CATSPER1):c.2126-13T>C	CATSPER1	Uncertain significance	criteria provided, single submitter
305417	NM_053054.4(CATSPER1):c.2109G>A (p.Thr703=)	CATSPER1	Uncertain significance	criteria provided, single submitter
305420	NM_053054.4(CATSPER1):c.2064+6G>A	CATSPER1	Uncertain significance	criteria provided, single submitter
305422	NM_053054.4(CATSPER1):c.1884G>A (p.Thr628=)	CATSPER1	Uncertain significance	criteria provided, single submitter
305423	NM_053054.4(CATSPER1):c.1748T>G (p.Ile583Ser)	CATSPER1	Uncertain significance	criteria provided, multiple submitters, no conflicts
305425	NM_053054.4(CATSPER1):c.1544-10G>A	CATSPER1	Uncertain significance	criteria provided, single submitter
305426	NM_053054.4(CATSPER1):c.1544-11C>T	CATSPER1	Uncertain significance	criteria provided, single submitter
305427	NM_053054.4(CATSPER1):c.1542G>A (p.Leu514=)	CATSPER1	Uncertain significance	criteria provided, single submitter
305428	NM_053054.4(CATSPER1):c.1514C>T (p.Ser505Leu)	CATSPER1	Uncertain significance	criteria provided, multiple submitters, no conflicts
305430	NM_053054.4(CATSPER1):c.1445C>G (p.Ala482Gly)	CATSPER1	Uncertain significance	criteria provided, single submitter
305431	NM_053054.4(CATSPER1):c.1444G>A (p.Ala482Thr)	CATSPER1	Uncertain significance	criteria provided, single submitter
305432	NM_053054.4(CATSPER1):c.1384G>A (p.Val462Ile)	CATSPER1	Uncertain significance	criteria provided, single submitter
305434	NM_053054.4(CATSPER1):c.1195G>A (p.Gly399Arg)	CATSPER1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CATSPER1	Limited	Unknown	spermatogenic failure 7	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CATSPER1	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder
STRC	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
STRC	Orphanet:94064	Deafness-infertility syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CATSPER1	HGNC:17116	ENSG00000175294	Q8NEC5	Cation channel sperm-associated protein 1	gencc,clinvar
STRC	HGNC:16035	ENSG00000242866	Q7RTU9	Stereocilin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CATSPER1	Cation channel sperm-associated protein 1	Pore-forming subunit of the CatSper complex, a sperm-specific voltage-gated calcium channel that plays a central role in calcium-dependent physiological responses essential for successful fertilization, such as sperm hyperactivation, acros…
STRC	Stereocilin	Essential to the formation of horizontal top connectors between outer hair cell stereocilia.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	1	55.8×	0.036
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CATSPER1	Ion channel	yes		Ion_trans_dom, Volt_channel_dom_sf, CatSper1
STRC	Other/Unknown	no		Stereocilin-rel, Stereocilin_LRR

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	1
male germ line stem cell (sensu Vertebrata) in testis	1
monocyte	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CATSPER1	135	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, monocyte, leukocyte
STRC	167		marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CATSPER1	1,621
STRC	1,152

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
STRC	Q7RTU9	69.21
CATSPER1	Q8NEC5	56.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Sperm Motility And Taxes	1	634.4×	0.008	CATSPER1
Sensory processing of sound	1	154.3×	0.015	STRC
Sensory processing of sound by outer hair cells of the cochlea	1	102.0×	0.015	STRC
Sensory processing of sound by inner hair cells of the cochlea	1	81.6×	0.015	STRC
Sensory Perception	1	47.6×	0.021	STRC

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of cilium beat frequency involved in ciliary motility	1	936.2×	0.007	CATSPER1
detection of mechanical stimulus involved in sensory perception of sound	1	468.1×	0.007	STRC
auditory receptor cell stereocilium organization	1	421.3×	0.007	STRC
calcium ion transport	1	90.6×	0.022	CATSPER1
cell-matrix adhesion	1	81.8×	0.022	STRC
flagellated sperm motility	1	58.5×	0.024	CATSPER1
intracellular protein localization	1	52.3×	0.024	STRC
spermatogenesis	1	17.6×	0.063	CATSPER1
cell differentiation	1	14.6×	0.068	CATSPER1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CATSPER1	0	0
STRC	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CATSPER1	5	Binding:5

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	CATSPER1
E	Difficult family or no structure, no drug	1	STRC

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CATSPER1	5	—
STRC	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.