MHC class II deficiency 4

Summary

MHC class II deficiency 4 (MONDO:0971015) is a disease caused by RFXAP (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: RFXAP (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	MHC class II deficiency 4
Mondo ID	MONDO:0971015
OMIM	620817
UMLS	C1859537
MedGen	347176
GARD	0027108
Is cancer (heuristic)	no

Data availability: 12 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 › immunodeficiency disease › combined immunodeficiency › severe combined immunodeficiency › familial severe combined immunodeficiency › MHC class II deficiency › MHC class II deficiency 4

Related subtypes (4): MHC class II deficiency 1, MHC class II deficiency 2, MHC class II deficiency 3, MHC class II deficiency 5

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

12 retrieved; paginated sample, class counts are floors:

7 pathogenic, 3 likely pathogenic, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
566425	NM_000538.4(RFXAP):c.127C>T (p.Gln43Ter)	LOC130009573	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3236735	NM_000538.4(RFXAP):c.350del (p.His117fs)	RFXAP	Pathogenic	no assertion criteria provided
3236736	NM_000538.4(RFXAP):c.467del (p.Gln156fs)	RFXAP	Pathogenic	no assertion criteria provided
3236737	NM_000538.4(RFXAP):c.219C>G (p.Tyr73Ter)	RFXAP	Pathogenic	no assertion criteria provided
3575883	NM_000538.4(RFXAP):c.259del (p.Glu87fs)	RFXAP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7649	NM_000538.4(RFXAP):c.302dup (p.Gly102fs)	RFXAP	Pathogenic	no assertion criteria provided
7650	NM_000538.4(RFXAP):c.392dup (p.Ser132fs)	RFXAP	Pathogenic	no assertion criteria provided
7651	NM_000538.4(RFXAP):c.368del (p.Ser123fs)	RFXAP	Pathogenic	criteria provided, multiple submitters, no conflicts
7652	NM_000538.4(RFXAP):c.163C>T (p.Gln55Ter)	RFXAP	Pathogenic	no assertion criteria provided
208152	NM_000538.4(RFXAP):c.323T>A (p.Leu108Ter)	RFXAP	Likely pathogenic	criteria provided, single submitter
3575882	NM_000538.4(RFXAP):c.52_100del (p.Val18fs)	RFXAP	Likely pathogenic	criteria provided, single submitter
3575885	NM_000538.4(RFXAP):c.696_700del (p.Asn232fs)	RFXAP	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
RFXAP	Strong	Autosomal recessive	MHC class II deficiency	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RFXAP	Orphanet:572	Immunodeficiency by defective expression of MHC class II

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
RFXAP	HGNC:9988	ENSG00000133111	O00287	Regulatory factor X-associated protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RFXAP	Regulatory factor X-associated protein	Part of the RFX complex that binds to the X-box of MHC II promoters.

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)
RFXAP	Other/Unknown	no		RFXAP_RFXANK-bd, RFXAP_C_sf

Expression context

Cohort genes with no expression data: 0.

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
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RFXAP	231	ubiquitous	yes	primordial germ cell in gonad, tendon of biceps brachii, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RFXAP	539

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RFXAP	O00287	1

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
positive regulation of MHC class II biosynthetic process	1	1203.7×	0.002	RFXAP
positive regulation of transcription by RNA polymerase II	1	14.9×	0.086	RFXAP
regulation of transcription by RNA polymerase II	1	11.7×	0.086	RFXAP

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
RFXAP	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	RFXAP

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)
RFXAP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.