Anal melanoma

Summary

Anal melanoma (MONDO:0006081) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver) and 1 clinical trial. Molecularly, KIT Internal Duplication confers sensitivity to Imatinib in Malignant Anus Melanoma (CIViC Level C). Top therapeutic interventions include cabozantinib.

At a glance

• Classification: Cancer
• Cohort genes: 1
• Clinical trials: 1
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	anal melanoma
Mondo ID	MONDO:0006081
EFO	EFO:1000080
DOID	DOID:14145
NCIT	C4639
SNOMED CT	276821000
UMLS	C0349538
MedGen	91151
GARD	0024285
Anatomy (UBERON)	UBERON:0001245
Is cancer (heuristic)	yes

Also known as: anal malignant melanoma · anal melanoma · anus melanoma · anus melanoma (disease) · malignant anus melanoma · malignant melanoma of anus · malignant melanoma of the anus · melanoma (disease) of anus · melanoma of anus · melanoma of the anus

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › large intestine disorder › rectal disorder › rectal neoplasm › anus neoplasm › anus cancer › anal melanoma

Related subtypes (3): anus lymphoma, anus sarcoma, anal carcinoma

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 18 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
KIT	Act	AML,GIST,MEL,MGCT	CIViC #29

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KIT	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
KIT	Orphanet:158766	Typical urticaria pigmentosa
KIT	Orphanet:158769	Plaque-form urticaria pigmentosa
KIT	Orphanet:158772	Nodular urticaria pigmentosa
KIT	Orphanet:158775	Smoldering systemic mastocytosis
KIT	Orphanet:158778	Isolated bone marrow mastocytosis
KIT	Orphanet:280785	Bullous diffuse cutaneous mastocytosis
KIT	Orphanet:280794	Pseudoxanthomatous diffuse cutaneous mastocytosis
KIT	Orphanet:2884	Piebaldism
KIT	Orphanet:44890	Gastrointestinal stromal tumor
KIT	Orphanet:566393	Acute mast cell leukemia
KIT	Orphanet:566396	Chronic mast cell leukemia
KIT	Orphanet:79455	Cutaneous mastocytoma
KIT	Orphanet:842	Testicular seminomatous germ cell tumor
KIT	Orphanet:90389	Telangiectasia macularis eruptiva perstans
KIT	Orphanet:98829	Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)
KIT	Orphanet:98834	Acute myeloblastic leukemia with maturation
KIT	Orphanet:98849	Systemic mastocytosis with associated hematologic neoplasm

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KIT	HGNC:6342	ENSG00000157404	P10721	Mast/stem cell growth factor receptor Kit	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIT	Mast/stem cell growth factor receptor Kit	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell develo…

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KIT	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_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
lateral nuclear group of thalamus	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIT	263	broad	marker	lateral nuclear group of thalamus, secondary oocyte, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIT	6,087

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIT	P10721	52

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 39. 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
Dasatinib-resistant KIT mutants	1	11420.0×	3e-04	KIT
Imatinib-resistant KIT mutants	1	11420.0×	3e-04	KIT
KIT mutants bind TKIs	1	11420.0×	3e-04	KIT
Masitinib-resistant KIT mutants	1	11420.0×	3e-04	KIT
Nilotinib-resistant KIT mutants	1	11420.0×	3e-04	KIT
Regorafenib-resistant KIT mutants	1	11420.0×	3e-04	KIT
Signaling by kinase domain mutants of KIT	1	11420.0×	3e-04	KIT
Sunitinib-resistant KIT mutants	1	11420.0×	3e-04	KIT
Signaling by juxtamembrane domain KIT mutants	1	11420.0×	3e-04	KIT
Sorafenib-resistant KIT mutants	1	11420.0×	3e-04	KIT
Drug resistance of KIT mutants	1	11420.0×	3e-04	KIT
Signaling by extracellular domain mutants of KIT	1	11420.0×	3e-04	KIT
Signaling by KIT in disease	1	1142.0×	0.003	KIT
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	761.3×	0.004	KIT
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	634.4×	0.004	KIT
Developmental Lineage of Mammary Gland Alveolar Cells	1	634.4×	0.004	KIT
Regulation of KIT signaling	1	601.0×	0.004	KIT
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	1	519.1×	0.004	KIT
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	456.8×	0.004	KIT
PI3K/AKT Signaling in Cancer	1	368.4×	0.005	KIT
Negative regulation of the PI3K/AKT network	1	278.5×	0.007	KIT
Signaling by SCF-KIT	1	248.3×	0.007	KIT
Transcriptional and post-translational regulation of MITF-M expression and activity	1	178.4×	0.010	KIT
MAPK1/MAPK3 signaling	1	131.3×	0.012	KIT
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.012	KIT
MITF-M-regulated melanocyte development	1	114.2×	0.013	KIT
MAPK family signaling cascades	1	102.9×	0.014	KIT
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.014	KIT
Intracellular signaling by second messengers	1	91.4×	0.015	KIT
PIP3 activates AKT signaling	1	66.8×	0.019	KIT

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
melanocyte adhesion	1	16852.0×	0.001	KIT
positive regulation of pyloric antrum smooth muscle contraction	1	16852.0×	0.001	KIT
positive regulation of colon smooth muscle contraction	1	16852.0×	0.001	KIT
positive regulation of vascular associated smooth muscle cell differentiation	1	8426.0×	0.001	KIT
Fc receptor signaling pathway	1	5617.3×	0.001	KIT
Kit signaling pathway	1	5617.3×	0.001	KIT
melanocyte migration	1	5617.3×	0.001	KIT
obsolete regulation of bile acid metabolic process	1	5617.3×	0.001	KIT
positive regulation of small intestine smooth muscle contraction	1	5617.3×	0.001	KIT
mast cell chemotaxis	1	4213.0×	0.001	KIT
hematopoietic stem cell migration	1	4213.0×	0.001	KIT
mast cell differentiation	1	4213.0×	0.001	KIT
positive regulation of dendritic cell cytokine production	1	3370.4×	0.001	KIT
positive regulation of mast cell cytokine production	1	3370.4×	0.001	KIT
mast cell proliferation	1	3370.4×	0.001	KIT
positive regulation of mast cell proliferation	1	3370.4×	0.001	KIT
lymphoid progenitor cell differentiation	1	2808.7×	0.001	KIT
erythropoietin-mediated signaling pathway	1	2808.7×	0.001	KIT
myeloid progenitor cell differentiation	1	2407.4×	0.001	KIT
immature B cell differentiation	1	2407.4×	0.001	KIT
glycosphingolipid metabolic process	1	2407.4×	0.001	KIT
tongue development	1	2106.5×	0.001	KIT
primordial germ cell migration	1	1872.4×	0.001	KIT
positive regulation of long-term neuronal synaptic plasticity	1	1872.4×	0.001	KIT
negative regulation of developmental process	1	1872.4×	0.001	KIT
negative regulation of reproductive process	1	1685.2×	0.002	KIT
positive regulation of pseudopodium assembly	1	1296.3×	0.002	KIT
embryonic hemopoiesis	1	991.3×	0.003	KIT
detection of mechanical stimulus involved in sensory perception of sound	1	936.2×	0.003	KIT
ectopic germ cell programmed cell death	1	842.6×	0.003	KIT

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
KIT	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KIT	99	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	KIT
FEDRATINIB	4	KIT
TIVOZANIB	4	KIT
LENVATINIB	4	KIT
AXITINIB	4	KIT
SORAFENIB	4	KIT
DASATINIB ANHYDROUS	4	KIT
NICLOSAMIDE	4	KIT
IMATINIB MESYLATE	4	KIT
RUXOLITINIB	4	KIT
INFIGRATINIB PHOSPHATE	4	KIT
INFIGRATINIB	4	KIT
REGORAFENIB	4	KIT
ENTRECTINIB	4	KIT
CABOZANTINIB	4	KIT
CERITINIB	4	KIT
VANDETANIB	4	KIT
NILOTINIB	4	KIT
BOSUTINIB	4	KIT
BRIGATINIB	4	KIT
PEXIDARTINIB	4	KIT
AVAPRITINIB	4	KIT
RIPRETINIB	4	KIT
PAZOPANIB	4	KIT
NINTEDANIB	4	KIT
SUNITINIB	4	KIT
DASATINIB	4	KIT
ERLOTINIB	4	KIT
QUIZARTINIB	4	KIT
CRIZOTINIB	4	KIT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KIT	2,305	Binding:2242, ADMET:32, Functional:22, Toxicity:9

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KIT	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
KIT	2,305

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

29 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.

Compound	Max phase	Cohort target (bioactivity)
PONATINIB	4	KIT
FEDRATINIB	4	KIT
TIVOZANIB	4	KIT
LENVATINIB	4	KIT
AXITINIB	4	KIT
SORAFENIB	4	KIT
DASATINIB ANHYDROUS	4	KIT
NICLOSAMIDE	4	KIT
IMATINIB MESYLATE	4	KIT
RUXOLITINIB	4	KIT
INFIGRATINIB PHOSPHATE	4	KIT
INFIGRATINIB	4	KIT
REGORAFENIB	4	KIT
ENTRECTINIB	4	KIT
CERITINIB	4	KIT
VANDETANIB	4	KIT
NILOTINIB	4	KIT
BOSUTINIB	4	KIT
BRIGATINIB	4	KIT
PEXIDARTINIB	4	KIT
AVAPRITINIB	4	KIT
RIPRETINIB	4	KIT
PAZOPANIB	4	KIT
NINTEDANIB	4	KIT
SUNITINIB	4	KIT
DASATINIB	4	KIT
ERLOTINIB	4	KIT
QUIZARTINIB	4	KIT
CRIZOTINIB	4	KIT

Druggability pyramid

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

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

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05111574	PHASE2	RECRUITING	Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CABOZANTINIB	4	3

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 1 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
KIT Internal Duplication	Imatinib	Sensitivity/Response	CIViC C	EID302