spermatogenic failure, X-linked, 9

Summary

spermatogenic failure, X-linked, 9 (MONDO:0976123) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spermatogenic failure, X-linked, 9
Mondo ID	MONDO:0976123
OMIM	301137
DOID	DOID:0061177
UMLS	C5974893
MedGen	1874423
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant · 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, X-linked, 9

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 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 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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3544365	NM_002893.4(RBBP7):c.1200dup (p.Trp401fs)	RBBP7	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 0 · 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
RBBP7	Limited	X-linked	spermatogenic failure, X-linked, 9

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
RBBP7	HGNC:9890	ENSG00000102054	Q16576	Histone-binding protein RBBP7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RBBP7	Histone-binding protein RBBP7	Core histone-binding subunit that may target chromatin remodeling factors, histone acetyltransferases and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RBBP7	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS

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
oocyte	1
right adrenal gland	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RBBP7	290	ubiquitous	marker	oocyte, secondary oocyte, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RBBP7	5,937

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RBBP7	Q16576	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 1 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
Regulation of TP53 Activity through Acetylation	1	456.8×	0.012	RBBP7
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1	380.7×	0.012	RBBP7
Transcriptional Regulation by E2F6	1	292.8×	0.012	RBBP7
RNA Polymerase I Transcription Initiation	1	223.9×	0.012	RBBP7
Regulation of PTEN gene transcription	1	178.4×	0.012	RBBP7
PKMTs methylate histone lysines	1	160.8×	0.012	RBBP7
Deposition of new CENPA-containing nucleosomes at the centromere	1	158.6×	0.012	RBBP7
Defective pyroptosis	1	156.4×	0.012	RBBP7
PRC2 methylates histones and DNA	1	152.3×	0.012	RBBP7
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	1	152.3×	0.012	RBBP7
RMTs methylate histone arginines	1	146.4×	0.012	RBBP7
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	146.4×	0.012	RBBP7
NuRD complex assembly	1	141.0×	0.012	RBBP7
Interaction of NuRD complexes with transcription factors	1	126.9×	0.012	RBBP7
HDACs deacetylate histones	1	120.2×	0.012	RBBP7
Negative Regulation of CDH1 Gene Transcription	1	120.2×	0.012	RBBP7
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	117.7×	0.012	RBBP7
Potential therapeutics for SARS	1	114.2×	0.012	RBBP7
Regulation of PD-L1(CD274) transcription	1	108.8×	0.012	RBBP7
Regulation of endogenous retroelements by KRAB-ZFP proteins	1	106.7×	0.012	RBBP7
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	91.4×	0.013	RBBP7
Oxidative Stress Induced Senescence	1	90.6×	0.013	RBBP7
HCMV Early Events	1	81.0×	0.013	RBBP7
HATs acetylate histones	1	79.3×	0.013	RBBP7
Neddylation	1	47.4×	0.021	RBBP7

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
cellular heat acclimation	1	3370.4×	0.004	RBBP7
regulation of cell fate specification	1	1296.3×	0.004	RBBP7
response to steroid hormone	1	842.6×	0.004	RBBP7
negative regulation of stem cell population maintenance	1	766.0×	0.004	RBBP7
regulation of stem cell differentiation	1	766.0×	0.004	RBBP7
positive regulation of stem cell population maintenance	1	343.9×	0.008	RBBP7
negative regulation of transforming growth factor beta receptor signaling pathway	1	173.7×	0.012	RBBP7
DNA replication	1	165.2×	0.012	RBBP7
negative regulation of cell growth	1	144.0×	0.012	RBBP7
negative regulation of cell migration	1	111.6×	0.014	RBBP7
brain development	1	79.5×	0.018	RBBP7
chromatin remodeling	1	73.0×	0.018	RBBP7
regulation of DNA-templated transcription	1	31.6×	0.036	RBBP7
negative regulation of DNA-templated transcription	1	31.6×	0.036	RBBP7
positive regulation of DNA-templated transcription	1	27.9×	0.038	RBBP7
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	RBBP7

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
RBBP7	RIBOFLAVIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RBBP7	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIBOFLAVIN	4	RBBP7
MOLIBRESIB	2	RBBP7

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RBBP7	19	Binding:19

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

2 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)
RIBOFLAVIN	4	RBBP7
MOLIBRESIB	2	RBBP7

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RBBP7
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.