Spermatocytic seminoma

Summary

Spermatocytic seminoma (MONDO:0020513) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 2

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	<1 / 1 000 000	0.03	Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	spermatocytic seminoma
Mondo ID	MONDO:0020513
Orphanet	99865
DOID	DOID:5834, DOID:7891
NCIT	C39921
UMLS	C0334517
MedGen	83159
GARD	0016921
Is cancer (heuristic)	no

Also known as: spermatocytic seminoma · testicular spermatocytic seminoma

Data availability: 2 ClinVar variants.

Disease family

Classification path: human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › germ cell tumor › gonadal germ cell tumor › testicular germ cell tumor › testicular pure germ cell tumor › testicular seminoma › spermatocytic seminoma

Related subtypes (3): tubular variant testicular seminoma, cribriform variant testicular seminoma, pseudoglandular variant testicular seminoma

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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
16331	NM_000142.5(FGFR3):c.1948A>G (p.Lys650Glu)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
12601	NM_005343.4(HRAS):c.181C>A (p.Gln61Lys)	HRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 18 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FGFR3	Orphanet:15	Achondroplasia
FGFR3	Orphanet:1860	Thanatophoric dysplasia type 1
FGFR3	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR3	Orphanet:251576	Gliosarcoma
FGFR3	Orphanet:251579	Giant cell glioblastoma
FGFR3	Orphanet:35099	Non-syndromic bicoronal craniosynostosis
FGFR3	Orphanet:429	Hypochondroplasia
FGFR3	Orphanet:53271	Muenke syndrome
FGFR3	Orphanet:794	Saethre-Chotzen syndrome
FGFR3	Orphanet:85164	Camptodactyly-tall stature-scoliosis-hearing loss syndrome
FGFR3	Orphanet:85165	Severe achondroplasia-developmental delay-acanthosis nigricans syndrome
FGFR3	Orphanet:93262	Crouzon syndrome-acanthosis nigricans syndrome
FGFR3	Orphanet:93274	Thanatophoric dysplasia type 2
HRAS	Orphanet:146	Differentiated thyroid carcinoma
HRAS	Orphanet:2612	Linear nevus sebaceus syndrome
HRAS	Orphanet:2874	Phakomatosis pigmentokeratotica
HRAS	Orphanet:3071	Costello syndrome
HRAS	Orphanet:79414	Woolly hair nevus

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
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	clinvar
HRAS	HGNC:5173	ENSG00000174775	P01112	GTPase HRas	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FGFR3	Fibroblast growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis.
HRAS	GTPase HRas	Involved in the activation of Ras protein signal transduction.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	13.9×	0.142
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
HRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type

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
skin of hip	1
upper arm skin	1
upper leg skin	1
skin of abdomen	1
skin of leg	1
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGFR3	262	broad	marker	upper leg skin, skin of hip, upper arm skin
HRAS	139	ubiquitous	marker	skin of abdomen, skin of leg, zone of skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HRAS	8,064
FGFR3	4,510

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HRAS	P01112	246
FGFR3	P22607	15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 80. 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
SHC-mediated cascade:FGFR3	2	601.0×	1e-04	FGFR3, HRAS
FRS-mediated FGFR3 signaling	2	543.8×	1e-04	FGFR3, HRAS
Signaling by FGFR3 in disease	2	496.5×	1e-04	FGFR3, HRAS
t(4;14) translocations of FGFR3	1	5710.0×	0.003	FGFR3
Signaling by FGFR3 fusions in cancer	1	5710.0×	0.003	FGFR3
RAF/MAP kinase cascade	2	61.1×	0.004	FGFR3, HRAS
Signaling by RAS GAP mutants	1	1903.3×	0.005	HRAS
Signaling by RAS GTPase mutants	1	1903.3×	0.005	HRAS
Activation of RAS in B cells	1	1142.0×	0.006	HRAS
FGFR3b ligand binding and activation	1	815.7×	0.006	FGFR3
RAS signaling downstream of NF1 loss-of-function variants	1	815.7×	0.006	HRAS
Estrogen-stimulated signaling through PRKCZ	1	815.7×	0.006	HRAS
SOS-mediated signalling	1	713.8×	0.006	HRAS
Activated NTRK3 signals through RAS	1	634.4×	0.006	HRAS
EGFR Transactivation by Gastrin	1	571.0×	0.006	HRAS
SHC-related events triggered by IGF1R	1	571.0×	0.006	HRAS
Activated NTRK2 signals through RAS	1	571.0×	0.006	HRAS
MET activates RAS signaling	1	519.1×	0.006	HRAS
Signaling by activated point mutants of FGFR3	1	475.8×	0.006	FGFR3
Signaling by FGFR4 in disease	1	475.8×	0.006	HRAS
Activated NTRK2 signals through FRS2 and FRS3	1	475.8×	0.006	HRAS
Constitutive Signaling by Overexpressed ERBB2	1	475.8×	0.006	HRAS
p38MAPK events	1	439.2×	0.006	HRAS
FGFR3c ligand binding and activation	1	439.2×	0.006	FGFR3
Phospholipase C-mediated cascade; FGFR3	1	439.2×	0.006	FGFR3
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	439.2×	0.006	HRAS
Signaling by PDGFRA extracellular domain mutants	1	439.2×	0.006	HRAS
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases	1	407.9×	0.006	HRAS
GRB2 events in EGFR signaling	1	380.7×	0.006	HRAS
Erythropoietin activates RAS	1	380.7×	0.006	HRAS

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
negative regulation of developmental growth	1	8426.0×	0.002	FGFR3
MAPK cascade	2	153.2×	0.002	FGFR3, HRAS
positive regulation of ERK1 and ERK2 cascade	2	85.1×	0.002	FGFR3, HRAS
positive regulation of MAPK cascade	2	80.6×	0.002	FGFR3, HRAS
fibroblast growth factor receptor apoptotic signaling pathway	1	4213.0×	0.003	FGFR3
bone maturation	1	2808.7×	0.003	FGFR3
positive regulation of miRNA metabolic process	1	2808.7×	0.003	HRAS
positive regulation of phospholipase activity	1	1685.2×	0.004	FGFR3
oncogene-induced cell senescence	1	1203.7×	0.005	HRAS
positive regulation of cell population proliferation	2	33.6×	0.005	FGFR3, HRAS
T-helper 1 type immune response	1	936.2×	0.006	HRAS
endochondral bone growth	1	842.6×	0.006	FGFR3
Schwann cell development	1	526.6×	0.007	HRAS
chondrocyte proliferation	1	526.6×	0.007	FGFR3
regulation of long-term neuronal synaptic plasticity	1	495.6×	0.007	HRAS
positive regulation of ruffle assembly	1	495.6×	0.007	HRAS
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	1	443.5×	0.008	HRAS
positive regulation of tyrosine phosphorylation of STAT protein	1	366.4×	0.009	FGFR3
defense response to protozoan	1	300.9×	0.009	HRAS
bone morphogenesis	1	300.9×	0.009	FGFR3
cellular response to gamma radiation	1	300.9×	0.009	HRAS
positive regulation of protein targeting to membrane	1	280.9×	0.009	HRAS
endochondral ossification	1	271.8×	0.009	FGFR3
positive regulation of wound healing	1	263.3×	0.009	HRAS
adipose tissue development	1	200.6×	0.011	HRAS
fibroblast proliferation	1	195.9×	0.011	HRAS
intrinsic apoptotic signaling pathway	1	179.3×	0.012	HRAS
chondrocyte differentiation	1	150.5×	0.013	FGFR3
positive regulation of fibroblast proliferation	1	147.8×	0.013	HRAS
cellular senescence	1	147.8×	0.013	HRAS

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
FGFR3	PONATINIB
HRAS	LONAFARNIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR3	64	4
HRAS	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	FGFR3
PEMIGATINIB	4	FGFR3
NINTEDANIB	4	FGFR3
FEDRATINIB	4	FGFR3
LENVATINIB	4	FGFR3
AXITINIB	4	FGFR3
SORAFENIB	4	FGFR3
INFIGRATINIB PHOSPHATE	4	FGFR3
INFIGRATINIB	4	FGFR3
ENTRECTINIB	4	FGFR3
CERITINIB	4	FGFR3
VANDETANIB	4	FGFR3
NINTEDANIB ESYLATE	4	FGFR3
BRIGATINIB	4	FGFR3
ERDAFITINIB	4	FGFR3
FUTIBATINIB	4	FGFR3
PAZOPANIB	4	FGFR3
SUNITINIB	4	FGFR3
DASATINIB	4	FGFR3
CRIZOTINIB	4	FGFR3
MIDOSTAURIN	4	FGFR3
LONAFARNIB	4	HRAS
LINIFANIB	3	FGFR3
SEMAXANIB	3	FGFR3
BRIVANIB	3	FGFR3
ALISERTIB	3	FGFR3
CEDIRANIB	3	FGFR3
DOVITINIB	3	FGFR3
LESTAURTINIB	3	FGFR3
TANDUTINIB	2	FGFR3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
FGFR3	975	Binding:948, Functional:18, ADMET:9
HRAS	48	Binding:45, Functional:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGFR3	2.7.10.1	receptor protein-tyrosine kinase
HRAS	3.6.5.2	small monomeric GTPase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
FGFR3	975

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

30 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.

Compound	Max phase	Cohort target (bioactivity)
PONATINIB	4	FGFR3
PEMIGATINIB	4	FGFR3
NINTEDANIB	4	FGFR3
FEDRATINIB	4	FGFR3
LENVATINIB	4	FGFR3
AXITINIB	4	FGFR3
SORAFENIB	4	FGFR3
INFIGRATINIB PHOSPHATE	4	FGFR3
INFIGRATINIB	4	FGFR3
ENTRECTINIB	4	FGFR3
CERITINIB	4	FGFR3
VANDETANIB	4	FGFR3
NINTEDANIB ESYLATE	4	FGFR3
BRIGATINIB	4	FGFR3
ERDAFITINIB	4	FGFR3
FUTIBATINIB	4	FGFR3
PAZOPANIB	4	FGFR3
SUNITINIB	4	FGFR3
DASATINIB	4	FGFR3
CRIZOTINIB	4	FGFR3
MIDOSTAURIN	4	FGFR3
LONAFARNIB	4	HRAS
LINIFANIB	3	FGFR3
SEMAXANIB	3	FGFR3
BRIVANIB	3	FGFR3
ALISERTIB	3	FGFR3
CEDIRANIB	3	FGFR3
DOVITINIB	3	FGFR3
LESTAURTINIB	3	FGFR3
TANDUTINIB	2	FGFR3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	FGFR3, HRAS
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.