Spermatogenic failure 77

Summary

Spermatogenic failure 77 (MONDO:0031083) is a disease caused by FKBP6 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: FKBP6 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spermatogenic failure 77
Mondo ID	MONDO:0031083
OMIM	620103
DOID	DOID:0070576
UMLS	C5774245
MedGen	1824018
Is cancer (heuristic)	no

Also known as: spermatogenic failure 77 · SPGF77

Data availability: 5 ClinVar variants · 2 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 77

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 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

5 retrieved; paginated sample, class counts are floors:

3 likely pathogenic, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1684032	NM_003602.5(FKBP6):c.589-2A>G	FKBP6	Pathogenic	criteria provided, single submitter
1684033	NM_003602.5(FKBP6):c.508_529dup (p.Phe177fs)	FKBP6	Pathogenic	criteria provided, single submitter
1683495	NM_003602.5(FKBP6):c.610C>T (p.Arg204Ter)	FKBP6	Likely pathogenic	criteria provided, single submitter
1684034	NM_003602.5(FKBP6):c.832C>T (p.Arg278Ter)	FKBP6	Likely pathogenic	criteria provided, single submitter
1684035	NM_003602.5(FKBP6):c.469-2A>T	FKBP6	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 5 · 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
FKBP10	Strong	Autosomal recessive	spermatogenic failure 77	11
FKBP6	Strong	Autosomal recessive	spermatogenic failure 77	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FKBP10	Orphanet:1149	Kuskokwim syndrome
FKBP10	Orphanet:216812	Osteogenesis imperfecta type 3
FKBP10	Orphanet:216820	Osteogenesis imperfecta type 4
FKBP10	Orphanet:2771	Bruck syndrome
FKBP6	Orphanet:904	Williams 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
FKBP10	HGNC:18169	ENSG00000141756	Q96AY3	Peptidyl-prolyl cis-trans isomerase FKBP10	gencc,clinvar
FKBP6	HGNC:3722	ENSG00000077800	O75344	Inactive peptidyl-prolyl cis-trans isomerase FKBP6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FKBP10	Peptidyl-prolyl cis-trans isomerase FKBP10	PPIases accelerate the folding of proteins during protein synthesis.
FKBP6	Inactive peptidyl-prolyl cis-trans isomerase FKBP6	Has an essential role in spermatogenesis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FKBP10	Other/Unknown	no		PPIase_FKBP_dom, EF_hand_dom, EF-hand-dom_pair
FKBP6	Other/Unknown	no		PPIase_FKBP_dom, TPR-like_helical_dom_sf, TPR_rpt

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
ascending aorta	1
stromal cell of endometrium	1
thoracic aorta	1
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FKBP10	179	ubiquitous	marker	stromal cell of endometrium, ascending aorta, thoracic aorta
FKBP6	161	tissue_specific	marker	left testis, right testis, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FKBP10	3,473
FKBP6	2,343

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FKBP6	O75344	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FKBP10	Q96AY3	89.19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PIWI-interacting RNA (piRNA) biogenesis	1	393.8×	0.005	FKBP6
Meiotic synapsis	1	141.0×	0.007	FKBP6

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
protein folding	2	103.4×	0.001	FKBP10, FKBP6
transposable element silencing by piRNA-mediated DNA methylation	1	561.7×	0.006	FKBP6
extracellular matrix assembly	1	468.1×	0.006	FKBP10
aorta morphogenesis	1	443.5×	0.006	FKBP10
piRNA processing	1	421.3×	0.006	FKBP6
regulatory ncRNA-mediated gene silencing	1	337.0×	0.006	FKBP6
positive regulation of viral genome replication	1	290.6×	0.006	FKBP6
meiotic cell cycle	1	122.1×	0.012	FKBP6
wound healing	1	113.9×	0.012	FKBP10
collagen fibril organization	1	112.3×	0.012	FKBP10
in utero embryonic development	1	36.0×	0.033	FKBP10
spermatogenesis	1	17.6×	0.061	FKBP6
cell differentiation	1	14.6×	0.068	FKBP6

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
FKBP10	0	0
FKBP6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
E	Difficult family or no structure, no drug	2	FKBP10, FKBP6

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)
FKBP10	0	—
FKBP6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.