Cutaneous mastocytosis
diseaseOn this page
Also known as CMCMCDcutaneous (skin) mastocytosiscutaneous mastocytosis (disease)mastocytosis, cutaneousmastocytosis, systemic, somatic
Summary
Cutaneous mastocytosis (MONDO:0019023) is a disease caused by KIT (GenCC Strong), with 14 cohort genes (25 GWAS associations across 3 studies) and 5 clinical trials.
At a glance
- Prevalence: Unknown (Worldwide) [Orphanet-validated]
- Causal gene: KIT (GenCC Strong)
- Cohort genes: 14
- GWAS associations: 25
- ClinVar variants: 42
- Clinical trials: 5
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | cutaneous mastocytosis |
| Mondo ID | MONDO:0019023 |
| EFO | EFO:1000886 |
| MeSH | D034701 |
| OMIM | 154800 |
| Orphanet | 66646 |
| DOID | DOID:3663 |
| ICD-10-CM | D47.01 |
| ICD-11 | 1300710062 |
| NCIT | C7137 |
| SNOMED CT | 397012002 |
| UMLS | C1136033 |
| MedGen | 210143 |
| GARD | 0007842 |
| Is cancer (heuristic) | no |
Also known as: CM · CMCD · cutaneous (skin) mastocytosis · cutaneous mastocytosis · cutaneous mastocytosis (disease) · mastocytosis, cutaneous · mastocytosis, systemic, somatic
Data availability: 42 ClinVar variants · 25 GWAS associations (3 studies) · 2 GenCC gene-disease records · 1 HPO phenotype · 1 cell line.
Disease family
An umbrella term covering 3 Mondo subtypes.
Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › skin neoplasm › dermis tumor › cutaneous mastocytosis
Related subtypes (7): cutaneous granular cell tumor, skin glomus tumor, leiomyoma cutis, malignant dermis tumor, cutaneous fibrous histiocytoma, juvenile hyaline fibromatosis, angioma serpiginosum
Subtypes (3): cutaneous mastocytoma, diffuse cutaneous mastocytosis, maculopapular cutaneous mastocytosis
Genetics & variants
GWAS landscape
25 GWAS associations across 3 studies. Top hits map to 21 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| rs80138802 | 2e-30 | ABCA2 | C | 6.97 |
| rs10838094 | 2e-25 | OR51B5, OR51Q1, HBG2, HBE1 | A | 0.16 |
| rs11845537 | 7e-22 | RPL3P3, OTX2-AS1, LINC03059 | A | 6.59 |
| rs9828758 | 5e-17 | PRDX5P1 - LINC02005 | T | 0.15 |
| rs2279343 | 6e-13 | CYP2B6 | G | 0.18 |
| rs7601511 | 3e-11 | TMEM182 - CRLF3P1 | G | 0.14 |
| rs76015112 | 4e-09 | RPTN | G | |
| rs1611207 | 1e-08 | HLA-F-AS1, HCG4, HLA-V, HLA-V | A | 2.01 |
| rs3218642 | 3e-08 | POLQ | T | 3.98 |
| rs8088340 | 4e-08 | MIR3976HG | C | 4.68 |
| rs1909936 | 6e-08 | FABP5 - PMP2 | C | 3.89 |
| rs1778155 | 8e-08 | PDE4DIP | T | 1.97 |
| rs41271217 | 1e-07 | DYNC2I1 | G | 4.49 |
| rs2728007 | 3e-07 | CNTN6 - RPL23AP38 | C | 3.75 |
| rs13195402 | 3e-07 | BTN2A1 | T | 2.8 |
| rs9530313 | 6e-07 | LINC00402 | A | 3.04 |
| rs973253 | 8e-07 | EGLN1 | C | 1.81 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST011381 | Nedoszytko B | 2020 | 141 | 5,606 | Results from a Genome-Wide Association Study (GWAS) in Mastocytosis Reveal New Gene Polymorphisms Associated with WHO Subgroups. |
| GCST011379 | Nedoszytko B | 2020 | 78 | 5,606 | Results from a Genome-Wide Association Study (GWAS) in Mastocytosis Reveal New Gene Polymorphisms Associated with WHO Subgroups. |
| GCST011380 | Nedoszytko B | 2020 | 65 | 5,606 | Results from a Genome-Wide Association Study (GWAS) in Mastocytosis Reveal New Gene Polymorphisms Associated with WHO Subgroups. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|---|
| Tier 1: coding | 6 |
| Tier 2: splice/UTR | 2 |
| Tier 3: regulatory | 0 |
| Tier 4: intronic/intergenic | 9 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 9 |
| low_freq (0.01-0.05) | 8 |
| rare (<0.01) | 0 |
| unknown | 0 |
Functional consequences
| Consequence | Count |
|---|---|
| missense_variant | 5 |
| intron_variant | 5 |
| intergenic_variant | 2 |
| synonymous_variant | 1 |
| non_coding_transcript_exon_variant | 1 |
| splice_polypyrimidine_tract_variant | 1 |
| splice_donor_5th_base_variant | 1 |
| stop_gained | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| rs80138802 | 9 | 137021488 | A>C,G | 0.024 | synonymous_variant | ABCA2 | 2e-30 | Tier 4: intronic/intergenic |
| rs10838094 | 11 | 5422663 | G>A,C | 0.411 | missense_variant | OR51B5, OR51Q1, HBG2, HBE1 | 2e-25 | Tier 1: coding |
| rs11845537 | 14 | 56979555 | G>A,C | 0.015 | non_coding_transcript_exon_variant | RPL3P3, OTX2-AS1, LINC03059 | 7e-22 | Tier 4: intronic/intergenic |
| rs9828758 | 3 | 73668985 | C>G,T | 0.293 | intergenic_variant | PRDX5P1 - LINC02005 | 5e-17 | Tier 4: intronic/intergenic |
| rs2279343 | 19 | 41009358 | A>G,T | 0.248 | missense_variant | CYP2B6 | 6e-13 | Tier 1: coding |
| rs7601511 | 2 | 103382339 | C>G | 0.214 | intron_variant | TMEM182 - CRLF3P1 | 3e-11 | Tier 4: intronic/intergenic |
| rs76015112 | 1 | 152156618 | A>G,T | 0.214 | missense_variant | RPTN | 4e-09 | Tier 1: coding |
| rs1611207 | 6 | 29792099 | G>A,C,T | 0.381 | splice_polypyrimidine_tract_variant | HLA-F-AS1, HCG4, HLA-V, HLA-V | 1e-08 | Tier 2: splice/UTR |
| rs3218642 | 3 | 121488790 | G>A,C,T | 0.028 | missense_variant | POLQ | 3e-08 | Tier 1: coding |
| rs8088340 | 18 | 5836383 | T>C,G | 0.017 | intron_variant | MIR3976HG | 4e-08 | Tier 4: intronic/intergenic |
| rs1909936 | 8 | 81333216 | T>C | 0.029 | intron_variant | FABP5 - PMP2 | 6e-08 | Tier 4: intronic/intergenic |
| rs1778155 | 1 | 149009657 | A>G | 0.454 | missense_variant | PDE4DIP | 8e-08 | Tier 1: coding |
| rs41271217 | 7 | 158914326 | A>G | 0.023 | splice_donor_5th_base_variant | DYNC2I1 | 1e-07 | Tier 2: splice/UTR |
| rs2728007 | 3 | 1545467 | C>G,T | 0.028 | intergenic_variant | CNTN6 - RPL23AP38 | 3e-07 | Tier 4: intronic/intergenic |
| rs13195402 | 6 | 26463347 | G>A,C,T | 0.036 | stop_gained | BTN2A1 | 3e-07 | Tier 1: coding |
| rs9530313 | 13 | 74424521 | A>C,G,T | 0.051 | intron_variant | LINC00402 | 6e-07 | Tier 4: intronic/intergenic |
| rs973253 | 1 | 231385128 | C>G,T | 0.299 | intron_variant | EGLN1 | 8e-07 | Tier 4: intronic/intergenic |
ClinVar germline variants
42 retrieved; paginated sample, class counts are floors:
20 uncertain significance, 16 conflicting classifications of pathogenicity, 2 likely benign, 2 pathogenic, 1 pathogenic/likely pathogenic, 1 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 13865 | NM_000222.3(KIT):c.1676T>C (p.Val559Ala) | KIT | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 375930 | NM_000222.3(KIT):c.2465A>T (p.Asn822Ile) | KIT | Pathogenic | no assertion criteria provided |
| 545643 | NM_000222.3(KIT):c.1598C>A (p.Ala533Asp) | KIT | Pathogenic | no assertion criteria provided |
| 134627 | NM_000222.3(KIT):c.2866C>T (p.Arg956Trp) | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 13852 | NM_000222.3(KIT):c.2447A>T (p.Asp816Val) | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1500519 | NM_000222.3(KIT):c.1231+13A>T | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1694457 | NM_000222.3(KIT):c.590C>T (p.Ser197Leu) | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 225286 | NM_000222.3(KIT):c.464C>T (p.Pro155Leu) | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 237233 | NM_000222.3(KIT):c.1109A>G (p.Asn370Ser) | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 409715 | NM_000222.3(KIT):c.2920G>A (p.Asp974Asn) | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 409716 | NM_000222.3(KIT):c.2848G>A (p.Val950Met) | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 409722 | NM_000222.3(KIT):c.148G>T (p.Val50Leu) | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 409758 | NM_000222.3(KIT):c.2663G>A (p.Arg888Gln) | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 458965 | NM_000222.3(KIT):c.749A>G (p.Asn250Ser) | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 576610 | NM_000222.3(KIT):c.2836C>T (p.Arg946Ter) | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 857642 | NM_000222.3(KIT):c.2564A>G (p.Tyr855Cys) | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 858552 | NM_000222.3(KIT):c.867G>A (p.Met289Ile) | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 947788 | NM_000222.3(KIT):c.2138C>T (p.Ser713Phe) | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 953437 | NM_000222.3(KIT):c.555T>G (p.His185Gln) | KIT | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1016059 | NM_000222.3(KIT):c.1952T>A (p.Met651Lys) | KIT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1760097 | NM_000222.3(KIT):c.767A>G (p.Gln256Arg) | KIT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2568309 | NM_000222.3(KIT):c.1924A>C (p.Lys642Gln) | KIT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3382507 | NM_000222.3(KIT):c.2449A>T (p.Ile817Phe) | KIT | Uncertain significance | criteria provided, single submitter |
| 3590592 | NM_000222.3(KIT):c.458G>C (p.Gly153Ala) | KIT | Uncertain significance | criteria provided, single submitter |
| 3590593 | NM_000222.3(KIT):c.689C>T (p.Thr230Ile) | KIT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3590594 | NM_000222.3(KIT):c.1879C>G (p.Pro627Ala) | KIT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3590596 | NM_000222.3(KIT):c.2781G>T (p.Gln927His) | KIT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 409732 | NM_000222.3(KIT):c.1900C>T (p.Arg634Trp) | KIT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 409795 | NM_000222.3(KIT):c.793G>A (p.Gly265Ser) | KIT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 458867 | NM_000222.3(KIT):c.1344G>C (p.Gln448His) | KIT | Uncertain significance | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 15 · Orphanet: 23 · 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 |
|---|---|---|---|---|
| KIT | Strong | Autosomal dominant | mastocytosis | 15 |
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 |
| EGLN1 | Orphanet:247511 | Autosomal dominant secondary polycythemia |
| PRPF31 | Orphanet:791 | Retinitis pigmentosa |
| DYNC2I1 | Orphanet:474 | Jeune syndrome |
| DYNC2I1 | Orphanet:93271 | Short rib-polydactyly syndrome, Verma-Naumoff type |
| ABCA2 | Orphanet:88616 | Autosomal recessive non-syndromic intellectual disability |
Cohort genes → proteins
14 cohort genes, 11 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| gwas_only | 13 |
| multi_evidence | 1 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| KIT | HGNC:6342 | ENSG00000157404 | P10721 | Mast/stem cell growth factor receptor Kit | gencc,clinvar |
| BTN2A1 | HGNC:1136 | ENSG00000112763 | Q7KYR7 | Butyrophilin subfamily 2 member A1 | gwas |
| EGLN1 | HGNC:1232 | ENSG00000135766 | Q9GZT9 | Egl nine homolog 1 | gwas |
| OR51Q1 | HGNC:14851 | ENSG00000167360 | Q8NH59 | Olfactory receptor 51Q1 | gwas |
| PRPF31 | HGNC:15446 | ENSG00000105618 | Q8WWY3 | U4/U6 small nuclear ribonucleoprotein Prp31 | gwas |
| PDE4DIP | HGNC:15580 | ENSG00000178104 | Q5VU43 | Myomegalin | gwas |
| DYNC2I1 | HGNC:21862 | ENSG00000126870 | Q8WVS4 | Cytoplasmic dynein 2 intermediate chain 1 | gwas |
| HLA-V | HGNC:23482 | ENSG00000181126 | major histocompatibility complex, class I, V (pseudogene) | gwas | |
| CYP2B6 | HGNC:2615 | ENSG00000197408 | P20813 | Cytochrome P450 2B6 | gwas |
| RPTN | HGNC:26809 | ENSG00000215853 | Q6XPR3 | Repetin | gwas |
| ABCA2 | HGNC:32 | ENSG00000107331 | Q9BZC7 | ATP-binding cassette sub-family A member 2 | gwas |
| LINC00402 | HGNC:42732 | ENSG00000235532 | long intergenic non-protein coding RNA 402 | gwas | |
| OTX2-AS1 | HGNC:43906 | ENSG00000248550 | OTX2 antisense RNA 1 | gwas | |
| POLQ | HGNC:9186 | ENSG00000051341 | O75417 | DNA polymerase theta | gwas |
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… |
| EGLN1 | Egl nine homolog 1 | Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. |
| OR51Q1 | Olfactory receptor 51Q1 | Odorant receptor. |
| PRPF31 | U4/U6 small nuclear ribonucleoprotein Prp31 | Involved in pre-mRNA splicing as component of the spliceosome. |
| PDE4DIP | Myomegalin | Functions as an anchor sequestering components of the cAMP-dependent pathway to Golgi and/or centrosomes. |
| DYNC2I1 | Cytoplasmic dynein 2 intermediate chain 1 | Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the i… |
| CYP2B6 | Cytochrome P450 2B6 | A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids. |
| RPTN | Repetin | Involved in the cornified cell envelope formation. |
| ABCA2 | ATP-binding cassette sub-family A member 2 | Probable lipid transporter that modulates cholesterol sequestration in the late endosome/lysosome by regulating the intracellular sphingolipid metabolism, in turn participates in cholesterol homeostasis. |
| POLQ | DNA polymerase theta | Low-fidelity DNA polymerase with a helicase activity that promotes microhomology-mediated end-joining (MMEJ), an alternative non-homologous end-joining (NHEJ) machinery required to repair double-strand breaks in DNA during mitosis. |
Protein-family classification
Druggable: 5 · Difficult: 2 · Unknown: 7 · Druggable fraction: 0.36
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 |
|---|---|---|---|
| Transporter | 1 | 5.6× | 0.836 |
| Antibody/Immunoglobulin | 1 | 2.1× | 0.836 |
| Kinase | 1 | 2.0× | 0.836 |
| GPCR | 1 | 1.7× | 0.836 |
| Scaffold/PPI | 1 | 1.2× | 0.836 |
| Other/Unknown | 7 | 0.9× | 0.836 |
| Enzyme (other) | 1 | 0.9× | 0.836 |
| Transcription factor | 1 | 0.6× | 0.836 |
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 |
| BTN2A1 | Antibody/Immunoglobulin | yes | B30.2/SPRY, Ig_sub, SPRY_dom | |
| EGLN1 | Transcription factor | no | 1.14.11.2 | Znf_MYND, Oxoglu/Fe-dep_dioxygenase_dom, Pro_4_hyd_alph |
| OR51Q1 | GPCR | yes | GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM | |
| PRPF31 | Other/Unknown | no | Nop_dom, NOSIC, Prp31_C | |
| PDE4DIP | Other/Unknown | no | Olduvai_dom, Cnn_1N, MT-associated_AKAP9-binding | |
| DYNC2I1 | Scaffold/PPI | no | WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf | |
| HLA-V | Other/Unknown | no | ||
| CYP2B6 | Enzyme (other) | yes | 1.14.14.1 | Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_E_grp-I_CYP2B-like |
| RPTN | Other/Unknown | no | S100/CaBP7/8-like_CS, EF_hand_dom, EF-hand-dom_pair | |
| ABCA2 | Transporter | yes | ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM | |
| LINC00402 | Other/Unknown | no | ||
| OTX2-AS1 | Other/Unknown | no | ||
| POLQ | Other/Unknown | no | DNA-dir_DNA_pol_A_palm_dom, Helicase_C-like, DNA_polymerase_A |
Expression context
Cohort genes with no expression data: 0.
12 cohort genes are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 1 |
| moderate (6-20) | 0 |
| broad (>20) | 13 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | 4 |
| oocyte | 2 |
| secondary oocyte | 2 |
| granulocyte | 2 |
| gastrocnemius | 2 |
| sural nerve | 2 |
| apex of heart | 2 |
| buccal mucosa cell | 2 |
| lateral nuclear group of thalamus | 1 |
| cerebellar hemisphere | 1 |
| spleen | 1 |
| adrenal tissue | 1 |
| muscle of leg | 1 |
| calcaneal tendon | 1 |
| colonic epithelium | 1 |
| stromal cell of endometrium | 1 |
| ventricular zone | 1 |
| hindlimb stylopod muscle | 1 |
| right uterine tube | 1 |
| sperm | 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 |
| BTN2A1 | 286 | ubiquitous | marker | granulocyte, spleen, cerebellar hemisphere |
| EGLN1 | 214 | ubiquitous | marker | gastrocnemius, muscle of leg, adrenal tissue |
| OR51Q1 | 2 | yes | sural nerve, colonic epithelium, calcaneal tendon | |
| PRPF31 | 134 | ubiquitous | marker | stromal cell of endometrium, granulocyte, ventricular zone |
| PDE4DIP | 292 | ubiquitous | marker | apex of heart, hindlimb stylopod muscle, gastrocnemius |
| DYNC2I1 | 269 | ubiquitous | marker | sural nerve, right uterine tube, sperm |
| HLA-V | 128 | tissue_specific | yes | apex of heart, male germ line stem cell (sensu Vertebrata) in testis, upper lobe of left lung |
| CYP2B6 | 106 | tissue_specific | marker | right lobe of liver, liver, buccal mucosa cell |
| RPTN | 57 | tissue_specific | marker | gingiva, gingival epithelium, tongue |
| ABCA2 | 234 | ubiquitous | marker | C1 segment of cervical spinal cord, spinal cord, right hemisphere of cerebellum |
| LINC00402 | 74 | tissue_specific | marker | male germ line stem cell (sensu Vertebrata) in testis, testis, lymph node |
| OTX2-AS1 | 104 | broad | marker | buccal mucosa cell, pigmented layer of retina, male germ line stem cell (sensu Vertebrata) in testis |
| POLQ | 166 | ubiquitous | marker | secondary oocyte, oocyte, male germ line stem cell (sensu Vertebrata) in testis |
Protein interactions among cohort
Intra-cohort edges: 4.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| KIT | 6,087 |
| PRPF31 | 3,427 |
| PDE4DIP | 2,146 |
| EGLN1 | 2,107 |
| CYP2B6 | 1,954 |
| POLQ | 1,785 |
| ABCA2 | 1,678 |
| RPTN | 1,413 |
| DYNC2I1 | 955 |
| OR51Q1 | 160 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| ABCA2 | OR51Q1 | string_interaction |
| OR51Q1 | PDE4DIP | string_interaction |
| OR51Q1 | RPTN | string_interaction |
| PDE4DIP | PRPF31 | biogrid_interaction, intact |
Structural data
PDB: 7 · AlphaFold-only: 4 · No structure: 3
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| EGLN1 | Q9GZT9 | 64 |
| KIT | P10721 | 52 |
| BTN2A1 | Q7KYR7 | 33 |
| POLQ | O75417 | 33 |
| PRPF31 | Q8WWY3 | 30 |
| CYP2B6 | P20813 | 13 |
| DYNC2I1 | Q8WVS4 | 4 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| OR51Q1 | Q8NH59 | 85.83 |
| ABCA2 | Q9BZC7 | 71.46 |
| PDE4DIP | Q5VU43 | 58.74 |
| RPTN | Q6XPR3 | 42.63 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 56. Enrichment computed across 14 evidence-associated genes (10 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 10 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 | 1142.0× | 0.004 | KIT |
| Imatinib-resistant KIT mutants | 1 | 1142.0× | 0.004 | KIT |
| KIT mutants bind TKIs | 1 | 1142.0× | 0.004 | KIT |
| Masitinib-resistant KIT mutants | 1 | 1142.0× | 0.004 | KIT |
| Nilotinib-resistant KIT mutants | 1 | 1142.0× | 0.004 | KIT |
| Regorafenib-resistant KIT mutants | 1 | 1142.0× | 0.004 | KIT |
| Signaling by kinase domain mutants of KIT | 1 | 1142.0× | 0.004 | KIT |
| Sunitinib-resistant KIT mutants | 1 | 1142.0× | 0.004 | KIT |
| Signaling by juxtamembrane domain KIT mutants | 1 | 1142.0× | 0.004 | KIT |
| Sorafenib-resistant KIT mutants | 1 | 1142.0× | 0.004 | KIT |
| Drug resistance of KIT mutants | 1 | 1142.0× | 0.004 | KIT |
| Signaling by extracellular domain mutants of KIT | 1 | 1142.0× | 0.004 | KIT |
| Signaling by KIT in disease | 1 | 114.2× | 0.038 | KIT |
| CYP2E1 reactions | 1 | 95.2× | 0.040 | CYP2B6 |
| HDR through MMEJ (alt-NHEJ) | 1 | 87.8× | 0.040 | POLQ |
| Butyrophilin (BTN) family interactions | 1 | 87.8× | 0.040 | BTN2A1 |
| TFAP2 (AP-2) family regulates transcription of growth factors and their receptors | 1 | 76.1× | 0.042 | KIT |
| Fatty acids | 1 | 71.4× | 0.042 | CYP2B6 |
| Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 1 | 63.4× | 0.042 | KIT |
| Developmental Lineage of Mammary Gland Alveolar Cells | 1 | 63.4× | 0.042 | KIT |
| ABC transporters in lipid homeostasis | 1 | 60.1× | 0.042 | ABCA2 |
| Regulation of KIT signaling | 1 | 60.1× | 0.042 | KIT |
| Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants | 1 | 51.9× | 0.047 | KIT |
| Xenobiotics | 1 | 49.6× | 0.047 | CYP2B6 |
| Developmental Lineage of Mammary Gland Luminal Epithelial Cells | 1 | 45.7× | 0.049 | KIT |
| PI3K/AKT Signaling in Cancer | 1 | 36.8× | 0.058 | KIT |
| Negative regulation of the PI3K/AKT network | 1 | 27.9× | 0.073 | KIT |
| Signaling by SCF-KIT | 1 | 24.8× | 0.079 | KIT |
| Phase I - Functionalization of compounds | 1 | 22.0× | 0.086 | CYP2B6 |
| Intraflagellar transport | 1 | 20.0× | 0.090 | DYNC2I1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| glycosphingolipid metabolic process | 2 | 481.5× | 1e-03 | KIT, ABCA2 |
| negative regulation of intracellular cholesterol transport | 1 | 1685.2× | 0.010 | ABCA2 |
| negative regulation of phospholipid biosynthetic process | 1 | 1685.2× | 0.010 | ABCA2 |
| ribonucleoprotein complex localization | 1 | 1685.2× | 0.010 | PRPF31 |
| negative regulation of sphingolipid biosynthetic process | 1 | 1685.2× | 0.010 | ABCA2 |
| melanocyte adhesion | 1 | 1685.2× | 0.010 | KIT |
| positive regulation of pyloric antrum smooth muscle contraction | 1 | 1685.2× | 0.010 | KIT |
| positive regulation of colon smooth muscle contraction | 1 | 1685.2× | 0.010 | KIT |
| regulation of protein localization to cell periphery | 1 | 1685.2× | 0.010 | ABCA2 |
| negative regulation of steroid metabolic process | 1 | 842.6× | 0.011 | ABCA2 |
| ceramide translocation | 1 | 842.6× | 0.011 | ABCA2 |
| regulation of post-translational protein modification | 1 | 842.6× | 0.011 | ABCA2 |
| negative regulation of hypoxia-inducible factor-1alpha signaling pathway | 1 | 842.6× | 0.011 | EGLN1 |
| positive regulation of vascular associated smooth muscle cell differentiation | 1 | 842.6× | 0.011 | KIT |
| negative regulation of receptor-mediated endocytosis involved in cholesterol transport | 1 | 842.6× | 0.011 | ABCA2 |
| positive regulation of low-density lipoprotein particle receptor catabolic process | 1 | 561.7× | 0.011 | ABCA2 |
| Fc receptor signaling pathway | 1 | 561.7× | 0.011 | KIT |
| Kit signaling pathway | 1 | 561.7× | 0.011 | KIT |
| ketone metabolic process | 1 | 561.7× | 0.011 | CYP2B6 |
| melanocyte migration | 1 | 561.7× | 0.011 | KIT |
| regulation protein catabolic process at postsynapse | 1 | 561.7× | 0.011 | EGLN1 |
| obsolete regulation of bile acid metabolic process | 1 | 561.7× | 0.011 | KIT |
| positive regulation of small intestine smooth muscle contraction | 1 | 561.7× | 0.011 | KIT |
| ganglioside metabolic process | 1 | 421.3× | 0.012 | ABCA2 |
| mast cell chemotaxis | 1 | 421.3× | 0.012 | KIT |
| regulation of intracellular cholesterol transport | 1 | 421.3× | 0.012 | ABCA2 |
| hematopoietic stem cell migration | 1 | 421.3× | 0.012 | KIT |
| mast cell differentiation | 1 | 421.3× | 0.012 | KIT |
| positive regulation of dendritic cell cytokine production | 1 | 337.0× | 0.012 | KIT |
| sphingomyelin metabolic process | 1 | 337.0× | 0.012 | ABCA2 |
Therapeutics
Drug target analysis
Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 5 · Undrugged: 9
Druggability breadth: 6 of 14 evidence-associated genes (43%) 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 |
| EGLN1 | ROXADUSTAT |
| CYP2B6 | PAZOPANIB |
| POLQ | NOVOBIOCIN |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| KIT | 99 | 4 |
| CYP2B6 | 28 | 4 |
| EGLN1 | 11 | 4 |
| PRPF31 | 1 | 2 |
| POLQ | 1 | 4 |
| BTN2A1 | 0 | 0 |
| OR51Q1 | 0 | 0 |
| PDE4DIP | 0 | 0 |
| DYNC2I1 | 0 | 0 |
| HLA-V | 0 | 0 |
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 | CYP2B6, 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): 3.
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 |
| CYP2B6 | 861 | ADMET:851, Binding:10 |
| EGLN1 | 211 | Binding:211 |
| POLQ | 46 | Binding:46 |
| PRPF31 | 6 | Binding:6 |
| BTN2A1 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| KIT | 2.7.10.1 | receptor protein-tyrosine kinase |
| EGLN1 | 1.14.11.2, 1.14.11.29 | procollagen-proline 4-dioxygenase, hypoxia-inducible factor-proline dioxygenase |
| CYP2B6 | 1.14.14.1 | unspecific monooxygenase |
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 |
| EGLN1 | 211 |
| CYP2B6 | 861 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 12; with CPIC/DPWG dosing guidelines: 1.
Cohort genes with a CPIC/DPWG dosing guideline
| Symbol | CPIC guidelines |
|---|---|
| CYP2B6 | 1 |
Chemical tractability of cohort targets
30 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) |
|---|---|---|
| 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 | CYP2B6, 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) | 4 | KIT, EGLN1, CYP2B6, POLQ |
| B | Phased (≥1) drug, not yet approved | 1 | PRPF31 |
| C | Druggable family + PDB, no drug | 1 | BTN2A1 |
| D | Druggable family + AlphaFold only, no drug | 2 | OR51Q1, ABCA2 |
| E | Difficult family or no structure, no drug | 6 | PDE4DIP, DYNC2I1, HLA-V, RPTN, LINC00402, OTX2-AS1 |
Undrugged target profiles
9 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| BTN2A1 | 1 | — |
| OR51Q1 | 0 | — |
| PDE4DIP | 0 | — |
| DYNC2I1 | 0 | — |
| HLA-V | 0 | — |
| RPTN | 0 | — |
| ABCA2 | 0 | — |
| LINC00402 | 0 | — |
| OTX2-AS1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 5.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 4 |
| PHASE2 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00457288 | PHASE2 | COMPLETED | Efficacy and Safety of TF002 in Cutaneous Mastocytosis |
| NCT07142473 | Not specified | RECRUITING | Mastocytosis From Pediatric Age to Adulthood: Local Registry of Cutaneous and Systemic Mastocytosis |
| NCT02761473 | Not specified | COMPLETED | Cutaneous Mastocytosis in Children: Analysis of Somatic and Germline Mutations |
| NCT03632811 | Not specified | COMPLETED | Adaptation of the Questionnaire Regarding Patient’s Quality of Life With Mastocytosis in the French Language |
| NCT04377828 | Not specified | UNKNOWN | Improvement of Pigmented Skin Lesions in Patients With Mastocytosis After Performing 2 Sessions of Pigment Laser |