Immunodeficiency 105

Summary

Immunodeficiency 105 (MONDO:0800104) is a disease caused by PTPRC (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PTPRC (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 105
Mondo ID	MONDO:0800104
OMIM	619924
DOID	DOID:0061074
UMLS	C5677005
MedGen	1809425
GARD	0026436
Is cancer (heuristic)	no

Also known as: IMD105

Data availability: 22 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 › immunodeficiency 105

Related subtypes (13): severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency, MHC class II deficiency, reticular dysgenesis, T-B+ severe combined immunodeficiency due to gamma chain deficiency, T-B+ severe combined immunodeficiency due to JAK3 deficiency, severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive, severe combined immunodeficiency due to DCLRE1C deficiency, Omenn syndrome, immunodeficiency 104, Cernunnos-XLF deficiency, immunodeficiency 18, immunodeficiency 19, immunodeficiency 49

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

22 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 5 conflicting classifications of pathogenicity, 4 pathogenic, 3 likely pathogenic, 2 benign/likely benign, 1 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
14457	NM_002838.5(PTPRC):c.1450+1G>A	PTPRC	Pathogenic	no assertion criteria provided
14458	NM_002838.5(PTPRC):c.1090_1095del (p.Glu364_Tyr365del)	PTPRC	Pathogenic	no assertion criteria provided
1460093	NM_002838.5(PTPRC):c.308C>G (p.Ser103Ter)	PTPRC	Pathogenic	criteria provided, single submitter
2819338	NM_002838.5(PTPRC):c.2668C>T (p.Arg890Ter)	PTPRC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
60723	NM_002838.5(PTPRC):c.1624A>T (p.Lys542Ter)	PTPRC	Pathogenic	no assertion criteria provided
2432878	NM_002838.5(PTPRC):c.3897T>G (p.Ser1299Arg)	PTPRC	Likely pathogenic	criteria provided, single submitter
2911403	NM_002838.5(PTPRC):c.583+1G>T	PTPRC	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4077449	NM_002838.5(PTPRC):c.2807del (p.Asp936fs)	PTPRC	Likely pathogenic	criteria provided, single submitter
190992	NM_002838.5(PTPRC):c.3545T>C (p.Leu1182Ser)	PTPRC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
506974	NM_002838.5(PTPRC):c.1568A>T (p.Glu523Val)	PTPRC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
533069	NM_002838.5(PTPRC):c.3073-6A>G	PTPRC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
573532	NM_002838.5(PTPRC):c.260C>T (p.Pro87Leu)	PTPRC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626155	NM_002838.5(PTPRC):c.2142+7A>G	PTPRC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3576521	NM_002838.5(PTPRC):c.1604A>G (p.Lys535Arg)	PTPRC	Uncertain significance	criteria provided, single submitter
440228	NM_002838.5(PTPRC):c.982A>G (p.Ile328Val)	PTPRC	Uncertain significance	criteria provided, multiple submitters, no conflicts
450252	NM_002838.5(PTPRC):c.2490G>C (p.Leu830Phe)	PTPRC	Uncertain significance	criteria provided, multiple submitters, no conflicts
577072	NM_002838.5(PTPRC):c.700A>G (p.Asn234Asp)	PTPRC	Uncertain significance	criteria provided, multiple submitters, no conflicts
642812	NM_002838.5(PTPRC):c.347A>C (p.Gln116Pro)	PTPRC	Uncertain significance	criteria provided, multiple submitters, no conflicts
648796	NM_002838.5(PTPRC):c.1678G>A (p.Asp560Asn)	PTPRC	Uncertain significance	criteria provided, multiple submitters, no conflicts
138846	NM_002838.5(PTPRC):c.3402C>T (p.Pro1134=)	PTPRC	Benign	criteria provided, multiple submitters, no conflicts
378444	NM_002838.5(PTPRC):c.177C>G (p.Pro59=)	PTPRC	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
464444	NM_002838.5(PTPRC):c.577A>G (p.Thr193Ala)	PTPRC	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
PTPRC	Strong	Autosomal recessive	immunodeficiency 104	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PTPRC	Orphanet:169157	T-B+ severe combined immunodeficiency due to CD45 deficiency

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
PTPRC	HGNC:9666	ENSG00000081237	P08575	Receptor-type tyrosine-protein phosphatase C	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PTPRC	Receptor-type tyrosine-protein phosphatase C	Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor.

Protein-family classification

Druggable: 1 · 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
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PTPRC	Phosphatase	yes		PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat

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
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PTPRC	277	broad	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTPRC	6,849

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTPRC	P08575	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Other semaphorin interactions	1	601.0×	0.003	PTPRC
Phosphorylation of CD3 and TCR zeta chains	1	543.8×	0.003	PTPRC
Neutrophil degranulation	1	23.1×	0.043	PTPRC

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
plasma membrane raft distribution	1	16852.0×	0.002	PTPRC
positive regulation of antigen receptor-mediated signaling pathway	1	16852.0×	0.002	PTPRC
negative regulation of interleukin-4-mediated signaling pathway	1	8426.0×	0.002	PTPRC
positive regulation of hematopoietic stem cell migration	1	8426.0×	0.002	PTPRC
alpha-beta T cell proliferation	1	5617.3×	0.002	PTPRC
negative regulation of cell adhesion involved in substrate-bound cell migration	1	4213.0×	0.002	PTPRC
regulation of interleukin-8 production	1	4213.0×	0.002	PTPRC
regulation of T cell receptor signaling pathway	1	4213.0×	0.002	PTPRC
DN2 thymocyte differentiation	1	4213.0×	0.002	PTPRC
positive regulation of humoral immune response mediated by circulating immunoglobulin	1	3370.4×	0.002	PTPRC
positive regulation of Fc receptor mediated stimulatory signaling pathway	1	3370.4×	0.002	PTPRC
cell cycle phase transition	1	2808.7×	0.002	PTPRC
positive regulation of alpha-beta T cell proliferation	1	2808.7×	0.002	PTPRC
stem cell development	1	2407.4×	0.002	PTPRC
negative regulation of T cell mediated cytotoxicity	1	2106.5×	0.002	PTPRC
gamma-delta T cell differentiation	1	2106.5×	0.002	PTPRC
negative regulation of microglial cell activation	1	2106.5×	0.002	PTPRC
negative regulation of cytokine-mediated signaling pathway	1	1872.4×	0.002	PTPRC
positive regulation of gamma-delta T cell differentiation	1	1872.4×	0.002	PTPRC
regulation of phagocytosis	1	1685.2×	0.002	PTPRC
response to aldosterone	1	1685.2×	0.002	PTPRC
positive regulation of isotype switching to IgG isotypes	1	1532.0×	0.002	PTPRC
bone marrow development	1	1532.0×	0.002	PTPRC
positive thymic T cell selection	1	1404.3×	0.002	PTPRC
negative thymic T cell selection	1	1404.3×	0.002	PTPRC
natural killer cell differentiation	1	887.0×	0.003	PTPRC
negative regulation of receptor signaling pathway via JAK-STAT	1	887.0×	0.003	PTPRC
negative regulation of protein kinase activity	1	842.6×	0.003	PTPRC
dephosphorylation	1	674.1×	0.003	PTPRC
positive regulation of protein kinase activity	1	674.1×	0.003	PTPRC

Therapeutics

Drug target analysis

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

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
PTPRC	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PTPRC	111	Binding:110, ADMET:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PTPRC	111

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	1	PTPRC
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
PTPRC	111	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.