subcutaneous panniculitis-like T-cell lymphoma

Summary

subcutaneous panniculitis-like T-cell lymphoma (MONDO:0019475) is a cancer caused by HAVCR2 (GenCC Definitive), with 1 cohort gene (1 CIViC-evidence somatic driver; 7 ClinVar predisposition records) and 9 clinical trials. Top therapeutic interventions include cyclophosphamide anhydrous, doxorubicin, and etoposide.

At a glance

• Classification: Cancer
• Prevalence: Unknown (Worldwide)
• Causal gene: HAVCR2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 7
• Phenotypes (HPO): 11
• Clinical trials: 9

Clinical features

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0012490	Panniculitis	Very frequent (80-99%)
HP:0030350	Erythematous papule	Very frequent (80-99%)
HP:0001433	Hepatosplenomegaly	Frequent (30-79%)
HP:0001824	Weight loss	Frequent (30-79%)
HP:0001945	Fever	Frequent (30-79%)
HP:0003256	Abnormality of the coagulation cascade	Frequent (30-79%)
HP:0012156	Hemophagocytosis	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0025143	Chills	Frequent (30-79%)
HP:0025474	Erythematous plaque	Frequent (30-79%)
HP:0200042	Skin ulcer	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	subcutaneous panniculitis-like T-cell lymphoma
Mondo ID	MONDO:0019475
EFO	EFO:1000552
MeSH	C537503
OMIM	618398
Orphanet	86884
DOID	DOID:0070662
ICD-10-CM	C86.3
ICD-11	1550338805
NCIT	C6918
SNOMED CT	404133000
UMLS	C0522624
MedGen	99306
GARD	0010193
Is cancer (heuristic)	yes

Also known as: SPTCL · subcutaneous panniculitic T-cell lymphoma · subcutaneous panniculitis-like T-cell lymphoma · subcutaneous panniculitis-like T-cell lymphoma (Alpha/Beta type) · subcutaneous panniculitis-like T-cell lymphoma, Alpha/Beta type

Data availability: 7 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › immune system cancer › subcutaneous panniculitis-like T-cell lymphoma

Related subtypes (24): lymphatic system cancer, T-cell childhood acute lymphocytic leukemia, B-cell childhood acute lymphoblastic leukemia, primary central nervous system lymphoma, thymus cancer, solitary plasmacytoma of chest wall, dendritic cell sarcoma, Waldeyer’s ring cancer, breast diffuse large B-cell lymphoma, colon Burkitt lymphoma, colorectal diffuse large B-cell lymphoma, gastric mantle cell lymphoma, liver diffuse large B-cell lymphoma, primary pulmonary diffuse large B-cell lymphoma, small intestinal Burkitt lymphoma, small intestinal diffuse large B-cell lymphoma, small intestinal enteropathy-associated T-cell lymphoma, thyroid gland diffuse large B-cell lymphoma, plasma cell myeloma, indolent primary cutaneous B-cell lymphoma, systemic Epstein-Barr virus-positive T-cell lymphoproliferative disease of childhood, mast cell sarcoma, bone marrow cancer, primary vitreoretinal large b-cell lymphoma

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

7 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 benign, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
626252	NM_032782.5(HAVCR2):c.245A>G (p.Tyr82Cys)	HAVCR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626253	NM_032782.5(HAVCR2):c.291A>G (p.Ile97Met)	HAVCR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1049012	NM_032782.5(HAVCR2):c.332G>A (p.Arg111Gln)	HAVCR2	Uncertain significance	no assertion criteria provided
2432364	NM_032782.5(HAVCR2):c.523-1G>A	HAVCR2	Uncertain significance	criteria provided, single submitter
4056793	NM_032782.5(HAVCR2):c.395-2A>T	HAVCR2	Uncertain significance	criteria provided, single submitter
1285330	NM_032782.5(HAVCR2):c.419G>T (p.Arg140Leu)	HAVCR2	Benign	criteria provided, multiple submitters, no conflicts
626254	NM_032782.5(HAVCR2):c.302C>T (p.Thr101Ile)	HAVCR2	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
HAVCR2			CIViC #16394

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
HAVCR2	Definitive	Autosomal recessive	subcutaneous panniculitis-like T-cell lymphoma	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HAVCR2	Orphanet:86884	Subcutaneous panniculitis-like T-cell lymphoma

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
HAVCR2	HGNC:18437	ENSG00000135077	Q8TDQ0	Hepatitis A virus cellular receptor 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HAVCR2	Hepatitis A virus cellular receptor 2	Cell surface receptor implicated in modulating innate and adaptive immune responses.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HAVCR2	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set

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
granulocyte	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HAVCR2	206	broad	marker	granulocyte, leukocyte, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HAVCR2	2,945

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HAVCR2	Q8TDQ0	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Interleukin-2 family signaling	1	634.4×	0.002	HAVCR2

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
regulation of tolerance induction dependent upon immune response	1	16852.0×	8e-04	HAVCR2
negative regulation of interleukin-3 production	1	16852.0×	8e-04	HAVCR2
negative regulation of granulocyte colony-stimulating factor production	1	16852.0×	8e-04	HAVCR2
natural killer cell tolerance induction	1	5617.3×	0.001	HAVCR2
negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target	1	5617.3×	0.001	HAVCR2
negative regulation of defense response to bacterium	1	5617.3×	0.001	HAVCR2
negative regulation of immunological synapse formation	1	5617.3×	0.001	HAVCR2
negative regulation of myeloid dendritic cell activation	1	4213.0×	0.001	HAVCR2
negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell	1	4213.0×	0.001	HAVCR2
negative regulation of T-helper 1 type immune response	1	3370.4×	0.001	HAVCR2
toll-like receptor 7 signaling pathway	1	3370.4×	0.001	HAVCR2
negative regulation of interferon-alpha production	1	2808.7×	0.001	HAVCR2
negative regulation of natural killer cell activation	1	2106.5×	0.001	HAVCR2
toll-like receptor 9 signaling pathway	1	1872.4×	0.001	HAVCR2
positive regulation of defense response to bacterium	1	1872.4×	0.001	HAVCR2
positive regulation of interleukin-1 production	1	1685.2×	0.001	HAVCR2
macrophage activation involved in immune response	1	1123.5×	0.002	HAVCR2
toll-like receptor 3 signaling pathway	1	1123.5×	0.002	HAVCR2
maternal process involved in female pregnancy	1	936.2×	0.002	HAVCR2
positive regulation of macrophage activation	1	842.6×	0.002	HAVCR2
negative regulation of interleukin-2 production	1	581.1×	0.003	HAVCR2
positive regulation of interleukin-4 production	1	561.7×	0.003	HAVCR2
negative regulation of type II interferon production	1	383.0×	0.004	HAVCR2
positive regulation of chemokine production	1	374.5×	0.004	HAVCR2
obsolete negative regulation of NF-kappaB transcription factor activity	1	358.6×	0.004	HAVCR2
negative regulation of interleukin-6 production	1	351.1×	0.004	HAVCR2
negative regulation of T cell proliferation	1	330.4×	0.004	HAVCR2
positive regulation of T cell proliferation	1	259.3×	0.005	HAVCR2
positive regulation of non-canonical NF-kappaB signal transduction	1	255.3×	0.005	HAVCR2
negative regulation of tumor necrosis factor production	1	251.5×	0.005	HAVCR2

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
HAVCR2	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
HAVCR2	13	Binding:13

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).

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

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	HAVCR2
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)
HAVCR2	13	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE2	2
PHASE1/PHASE2	2
PHASE4	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01746992	PHASE4	UNKNOWN	CTOP/ITE/MTX Compared With CHOP as the First-line Therapy for Newly Diagnosed Young Patients With T Cell Lymphoma
NCT03598998	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Pembrolizumab and Pralatrexate in Treating Patients With Relapsed or Refractory Peripheral T-Cell Lymphomas
NCT05475925	PHASE1/PHASE2	RECRUITING	A Study of DR-01 in Subjects With Large Granular Lymphocytic Leukemia or Cytotoxic Lymphomas
NCT02533700	PHASE2	UNKNOWN	CEOP/IVE/GDP Compared With CEOP as the First-line Therapy for Newly Diagnosed Adult Patients With PTCL
NCT04795869	PHASE2	WITHDRAWN	Brentuximab Vedotin and Pembrolizumab in Treating Patients With Recurrent Peripheral T-Cell Lymphoma
NCT01445535	PHASE1	COMPLETED	Phase 1 Trial of Siplizumab and Dose-Adjusted EPOCH-Rituximab in T- and NK-Cell Lymphomas
NCT01787409	Not specified	ACTIVE_NOT_RECRUITING	Cholecalciferol in Improving Survival in Patients With Newly Diagnosed Cancer With Vitamin D Insufficiency
NCT05978141	Not specified	RECRUITING	A Registry for People With T-cell Lymphoma
NCT02652715	Not specified	COMPLETED	Salvia Hispanica Seed in Reducing Risk of Disease Recurrence in Patients With Non-Hodgkin Lymphoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	3
DOXORUBICIN	4	3
ETOPOSIDE	4	1
IFOSFAMIDE	4	1
METHOTREXATE	4	1
PRALATREXATE	4	1
PREDNISONE	4	1
VINCRISTINE	4	1
PIRARUBICIN	3	1
DIBOTATUG	2	1
SIPLIZUMAB	2	1
CHEMBL15720	0	1
CHEMBL426	0	1