Spermatogenic failure 43

Summary

Spermatogenic failure 43 (MONDO:0032898) is a disease caused by SPEF2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SPEF2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spermatogenic failure 43
Mondo ID	MONDO:0032898
OMIM	618751
DOID	DOID:0111917
UMLS	C5231490
MedGen	1684830
GARD	0018414
Is cancer (heuristic)	no

Also known as: SPGF43

Data availability: 21 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › spermatogenic failure › spermatogenic failure 43

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 7, 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 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

21 retrieved; paginated sample, class counts are floors:

9 benign, 8 pathogenic, 2 uncertain significance, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3382335	NM_024867.4(SPEF2):c.2203C>T (p.Gln735Ter)	SPEF2	Pathogenic	criteria provided, single submitter
805986	NM_024867.4(SPEF2):c.13del (p.Leu5fs)	SPEF2	Pathogenic	no assertion criteria provided
805987	NM_024867.4(SPEF2):c.1745-2A>G	SPEF2	Pathogenic	no assertion criteria provided
805988	NM_024867.4(SPEF2):c.4102G>T (p.Glu1368Ter)	SPEF2	Pathogenic	no assertion criteria provided
805989	NM_024867.4(SPEF2):c.4326dup (p.Val1443fs)	SPEF2	Pathogenic	no assertion criteria provided
805990	NM_024867.4(SPEF2):c.2735del (p.Pro912fs)	SPEF2	Pathogenic	no assertion criteria provided
805991	NM_024867.4(SPEF2):c.4952del (p.Val1651fs)	SPEF2	Pathogenic	no assertion criteria provided
805992	NM_024867.4(SPEF2):c.3240del (p.Phe1080fs)	SPEF2	Pathogenic	no assertion criteria provided
2582765	NM_024867.4(SPEF2):c.1379A>G (p.His460Arg)	SPEF2	Uncertain significance	no assertion criteria provided
3362456	NM_024867.4(SPEF2):c.3063G>C (p.Glu1021Asp)	SPEF2	Uncertain significance	criteria provided, single submitter
1262331	NM_024867.4(SPEF2):c.1167+46T>C	SPEF2	Benign	criteria provided, multiple submitters, no conflicts
1273350	NM_024867.4(SPEF2):c.2914+19T>G	SPEF2	Benign	criteria provided, multiple submitters, no conflicts
403471	NM_024867.4(SPEF2):c.211A>C (p.Asn71His)	SPEF2	Benign	criteria provided, multiple submitters, no conflicts
403472	NM_024867.4(SPEF2):c.579T>C (p.Ile193=)	SPEF2	Benign	criteria provided, multiple submitters, no conflicts
403473	NM_024867.4(SPEF2):c.861C>T (p.Asp287=)	SPEF2	Benign	criteria provided, multiple submitters, no conflicts
403477	NM_024867.4(SPEF2):c.2142T>C (p.Asn714=)	SPEF2	Benign	criteria provided, multiple submitters, no conflicts
403478	NM_024867.4(SPEF2):c.2711C>T (p.Ala904Val)	SPEF2	Benign	criteria provided, multiple submitters, no conflicts
403479	NM_024867.4(SPEF2):c.2800G>C (p.Ala934Pro)	SPEF2	Benign	criteria provided, multiple submitters, no conflicts
403481	NM_024867.4(SPEF2):c.3331-11T>C	SPEF2	Benign	criteria provided, multiple submitters, no conflicts
727928	NM_024867.4(SPEF2):c.398G>A (p.Ser133Asn)	SPEF2	Likely benign	criteria provided, multiple submitters, no conflicts
769650	NM_024867.4(SPEF2):c.1633C>T (p.Pro545Ser)	SPEF2	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
SPEF2	Strong	Autosomal recessive	spermatogenic failure 43	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SPEF2	Orphanet:244	Primary ciliary dyskinesia
SPEF2	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SPEF2	HGNC:26293	ENSG00000152582	Q9C093	Sperm flagellar protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPEF2	Sperm flagellar protein 2	Required for correct axoneme development in spermatozoa.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SPEF2	Other/Unknown	no		CH_dom, CH_2, EF-hand-dom_pair

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
bronchus	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPEF2	181	ubiquitous	marker	right uterine tube, bronchial epithelial cell, bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPEF2	1,354

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SPEF2	Q9C093	71.30

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
respiratory system development	1	3370.4×	0.002	SPEF2
epithelial cilium movement involved in extracellular fluid movement	1	766.0×	0.003	SPEF2
brain morphogenesis	1	732.7×	0.003	SPEF2
skeletal system morphogenesis	1	495.6×	0.003	SPEF2
sperm axoneme assembly	1	468.1×	0.003	SPEF2
spermatogenesis	1	35.2×	0.028	SPEF2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SPEF2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	0
E	Difficult family or no structure, no drug	1	SPEF2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SPEF2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.