Multiple sclerosis, susceptibility to, 5

Summary

Multiple sclerosis, susceptibility to, 5 (MONDO:0013893) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	multiple sclerosis, susceptibility to, 5
Mondo ID	MONDO:0013893
OMIM	614810
UMLS	C3553728
MedGen	766642
Is cancer (heuristic)	no

Also known as: MS5 · multiple sclerosis, susceptibility to caused by mutation in TNFRSF1A · multiple sclerosis, susceptibility to, 5 · multiple sclerosis, susceptibility to, type 5 · TNFRSF1A multiple sclerosis, susceptibility to

Data availability: 3 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › multiple sclerosis, susceptibility to › multiple sclerosis, susceptibility to, 5

Related subtypes (4): multiple sclerosis, susceptibility to, 2, multiple sclerosis, susceptibility to, 3, multiple sclerosis, susceptibility to, 4, multiple sclerosis, susceptibility to 1

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

3 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 benign, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
217017	NM_001065.4(TNFRSF1A):c.362G>A (p.Arg121Gln)	TNFRSF1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
881907	NM_001065.4(TNFRSF1A):c.460G>A (p.Val154Met)	TNFRSF1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
37038	NM_001065.4(TNFRSF1A):c.625+10A>G	TNFRSF1A	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TNFRSF1A	Orphanet:32960	Tumor necrosis factor receptor 1 associated periodic syndrome
TNFRSF1A	Orphanet:329967	Intermittent hydrarthrosis

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
TNFRSF1A	HGNC:11916	ENSG00000067182	P19438	Tumor necrosis factor receptor superfamily member 1A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TNFRSF1A	Tumor necrosis factor receptor superfamily member 1A	Receptor for TNFSF2/TNF and homotrimeric TNFSF1/lymphotoxin-alpha.

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)
TNFRSF1A	Other/Unknown	no		Death_dom, TNFR/NGFR_Cys_rich_reg, DEATH-like_dom_sf

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
gall bladder	1
left uterine tube	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TNFRSF1A	292	ubiquitous	marker	tendon of biceps brachii, gall bladder, left uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNFRSF1A	4,523

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNFRSF1A	P19438	13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
TNFR1-mediated ceramide production	1	1903.3×	0.004	TNFRSF1A
TNFR1-induced proapoptotic signaling	1	439.2×	0.004	TNFRSF1A
TNF signaling	1	423.0×	0.004	TNFRSF1A
TNFs bind their physiological receptors	1	393.8×	0.004	TNFRSF1A
TNFR1-induced NF-kappa-B signaling pathway	1	335.9×	0.004	TNFRSF1A
Interleukin-10 signaling	1	233.1×	0.004	TNFRSF1A
Regulation of TNFR1 signaling	1	223.9×	0.004	TNFRSF1A

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
obsolete positive regulation of amide metabolic process	1	8426.0×	0.001	TNFRSF1A
positive regulation of apoptotic process involved in morphogenesis	1	5617.3×	0.001	TNFRSF1A
obsolete regulation of membrane lipid metabolic process	1	5617.3×	0.001	TNFRSF1A
pulmonary valve development	1	4213.0×	0.001	TNFRSF1A
negative regulation of extracellular matrix constituent secretion	1	4213.0×	0.001	TNFRSF1A
aortic valve development	1	3370.4×	0.001	TNFRSF1A
positive regulation of lipid metabolic process	1	3370.4×	0.001	TNFRSF1A
regulation of establishment of endothelial barrier	1	1872.4×	0.002	TNFRSF1A
negative regulation of cardiac muscle hypertrophy	1	1123.5×	0.003	TNFRSF1A
prostaglandin metabolic process	1	842.6×	0.003	TNFRSF1A
positive regulation of execution phase of apoptosis	1	842.6×	0.003	TNFRSF1A
regulation of tumor necrosis factor-mediated signaling pathway	1	702.2×	0.003	TNFRSF1A
extrinsic apoptotic signaling pathway via death domain receptors	1	401.2×	0.006	TNFRSF1A
canonical NF-kappaB signal transduction	1	366.4×	0.006	TNFRSF1A
tumor necrosis factor-mediated signaling pathway	1	330.4×	0.006	TNFRSF1A
intrinsic apoptotic signaling pathway in response to DNA damage	1	324.1×	0.006	TNFRSF1A
cell surface receptor signaling pathway via JAK-STAT	1	290.6×	0.006	TNFRSF1A
cellular response to mechanical stimulus	1	216.1×	0.007	TNFRSF1A
negative regulation of canonical NF-kappaB signal transduction	1	172.0×	0.009	TNFRSF1A
positive regulation of inflammatory response	1	145.3×	0.010	TNFRSF1A
negative regulation of inflammatory response	1	137.0×	0.010	TNFRSF1A
cytokine-mediated signaling pathway	1	130.6×	0.010	TNFRSF1A
protein polyubiquitination	1	115.4×	0.011	TNFRSF1A
protein localization to plasma membrane	1	108.7×	0.011	TNFRSF1A
defense response to bacterium	1	108.0×	0.011	TNFRSF1A
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.015	TNFRSF1A
transcription by RNA polymerase II	1	70.5×	0.015	TNFRSF1A
inflammatory response	1	37.7×	0.027	TNFRSF1A
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	TNFRSF1A

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TNFRSF1A	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
METOCHALCONE	2	TNFRSF1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TNFRSF1A	24	Binding:23, Functional:1

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

1 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)
METOCHALCONE	2	TNFRSF1A

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	1	TNFRSF1A
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.