Plasma cell myeloma

Summary

Plasma cell myeloma (MONDO:0009693) is a cancer with 75 cohort genes (229 GWAS associations across 37 studies; 38 CIViC-evidence somatic drivers; 90 ClinVar predisposition records) and 2,963 clinical trials. The dominant Reactome pathway is Gene expression (Transcription) (20 cohort genes). Molecularly, CTAG1B Overexpression confers sensitivity to Letetresgene Autoleucel in Multiple Myeloma (CIViC Level B); 20 further subtype–drug associations are mapped below. Top therapeutic interventions include bortezomib, carfilzomib, and pomalidomide.

At a glance

• Classification: Cancer
• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Cohort genes: 75
• GWAS associations: 229
• ClinVar variants: 90
• Phenotypes (HPO): 31
• Clinical trials: 2,963
• Precision-medicine evidence (CIViC): 21 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

9 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	6	Worldwide	Validated
Annual incidence	1-9 / 100 000	2.4	Europe	Validated
Point prevalence	1-5 / 10 000	11.9	Europe	Validated
Annual incidence	1-9 / 100 000	7.7	France	Validated
Annual incidence	1-9 / 100 000	5.6	United States	Validated
Annual incidence	1-9 / 100 000	2	Iran, Islamic Republic of	Validated
Annual incidence	1-9 / 100 000	5.1	Australia	Validated
Annual incidence	1-9 / 100 000	6.2	Denmark	Validated
Prevalence at birth	1-9 / 100 000	3.8	United States	Validated

Signs & symptoms

Clinical features (HPO)

31 HPO clinical features (Orphanet curated; top 31 by frequency):

HPO ID	Term	Frequency
HP:0000938	Osteopenia	Very frequent (80-99%)
HP:0002756	Pathologic fracture	Very frequent (80-99%)
HP:0000100	Nephrotic syndrome	Frequent (30-79%)
HP:0000112	Nephropathy	Frequent (30-79%)
HP:0000980	Pallor	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0001919	Acute kidney injury	Frequent (30-79%)
HP:0002152	Hyperproteinemia	Frequent (30-79%)
HP:0002653	Bone pain	Frequent (30-79%)
HP:0002797	Osteolysis	Frequent (30-79%)
HP:0003237	Increased circulating IgG level	Frequent (30-79%)
HP:0003259	Elevated circulating creatinine concentration	Frequent (30-79%)
HP:0003324	Generalized muscle weakness	Frequent (30-79%)
HP:0004313	Decreased circulating antibody level	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0000014	Abnormality of the bladder	Occasional (5-29%)
HP:0000098	Tall stature	Occasional (5-29%)
HP:0001824	Weight loss	Occasional (5-29%)
HP:0002176	Spinal cord compression	Occasional (5-29%)
HP:0002808	Kyphosis	Occasional (5-29%)
HP:0002953	Vertebral compression fracture	Occasional (5-29%)
HP:0003072	Hypercalcemia	Occasional (5-29%)
HP:0003261	Increased circulating IgA level	Occasional (5-29%)
HP:0003401	Paresthesia	Occasional (5-29%)
HP:0004341	Abnormality of vitamin B12 metabolism	Occasional (5-29%)
HP:0009830	Peripheral neuropathy	Occasional (5-29%)
HP:0012185	Constrictive median neuropathy	Occasional (5-29%)
HP:0012719	Functional abnormality of the gastrointestinal tract	Occasional (5-29%)
HP:0001744	Splenomegaly	Very rare (<1-4%)
HP:0002202	Pleural effusion	Very rare (<1-4%)
HP:0002716	Lymphadenopathy	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	plasma cell myeloma
Mondo ID	MONDO:0009693
EFO	EFO:0001378
MeSH	D009101
OMIM	254500
Orphanet	29073
DOID	DOID:9538
ICD-10-CM	C90.0
ICD-11	1582389689, 526287100
NCIT	C3242
UMLS	C0026764
MedGen	10122
GARD	0007108
MedDRA	10028228
NORD	1469
Is cancer (heuristic)	yes

Also known as: Kahler disease · Kahler’s disease · medullary plasmacytoma · Multiple Myeloma · multiple myeloma · multiple myeloma, resistance to, Somatic mutation · multiple myeloma, susceptibility to, Somatic mutation · multiple myeloma/plasma cell myeloma · myeloid neoplasm of plasma cell · myeloma · myeloma - multiple · myeloma, multiple · myeloma, plasma cell, malignant · myelomatosis · plasma cell myeloid neoplasm · plasma cell myeloma

Data availability: 90 ClinVar variants · 229 GWAS associations (37 studies) · 326 cell lines · 53 intOGen driver records.

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 › cancer › immune system cancer › plasma cell myeloma

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, indolent primary cutaneous B-cell lymphoma, systemic Epstein-Barr virus-positive T-cell lymphoproliferative disease of childhood, mast cell sarcoma, subcutaneous panniculitis-like T-cell lymphoma, bone marrow cancer, primary vitreoretinal large b-cell lymphoma

Subtypes (3): osteosclerotic plasma cell myeloma, non-secretory plasma cell myeloma, smoldering plasma cell myeloma

Genetics & variants

GWAS landscape

229 GWAS associations across 37 studies. Top hits map to 30 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs75341503	1e-35	DNAH11	A	1.25
rs5995688	3e-31	CBX7	G	1.21
rs7577599	8e-28	DTNB	T	1.27
rs139402	5e-26	CBX7	C	1.23
rs34562254	3e-23	TNFRSF13B	A	1.3
rs3132535	2e-22	CCHCR1	A	1.19
rs6546615	7e-22	NDUFB4P4 - KIF3C	G	1.21
rs9856633	2e-20	ULK4 - GEMIN2P2	A	1.23
rs4273077	2e-19	TNFRSF13B	?	1.24
rs10233479	5e-19	CHPF2	T	1.25
rs6599192	9e-18	ULK4	G	1.26
rs7621631	9e-18	LRRC34	C	1.18
rs4538746	2e-17	HLA-DQB1	T	1.22
rs9386514	2e-16	ATG5	C	1.18
rs3731222	3e-16	CDKN2A	T	1.23
rs877529	8e-16	CBX7	A	1.23
rs1948915	2e-15	CASC19, PCAT1	C	1.15
rs4487645	5e-15	DNAH11	C	1.26
rs10936600	6e-15	LRRC34	A	1.2
rs9372120	9e-15	ATG5	G	1.18
rs79502	2e-14	CBX7	?	1.21
rs12711846	3e-14	ACOXL, MIR4435-2HG, ACOXL-AS1	G
rs4525246	3e-14	GRAMD1B	C
rs544095130	4e-14	ELL2	?	0.87
rs10936599	9e-14	MYNN	G	1.26
rs6066835	1e-13	PREX1	C	1.26
rs13338946	1e-13	RNU6-416P - SRCAP	C	1.15
rs1716981	1e-13	ULK4	?	0.87
rs2811710	2e-13	CDKN2A	G	1.15
rs11085015	2e-13	NFIC	T	1.19

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90267403	Berndt SI	2022	13,763	18,862	Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes.
GCST90451657	Went M	2024	10,906	366,221	Deciphering the genetics and mechanisms of predisposition to multiple myeloma.
GCST90624746	Guler M	2025	9,609	1,223,020	Clustering of lymphoid neoplasms by cell of origin, somatic mutation and drug usage profiles: a multi-trait genome-wide association study.
GCST006432	Went M	2018	8,197	241,468	Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma.
GCST004483	Mitchell JS	2016	7,319	234,385	Genome-wide association study identifies multiple susceptibility loci for multiple myeloma.
GCST012396	Duran-Lozano L	2021	4,376	345,887	Germline variants at SOHLH2 influence multiple myeloma risk.
GCST012397	Duran-Lozano L	2021	4,376	422,293	Germline variants at SOHLH2 influence multiple myeloma risk.
GCST90624747	Guler M	2025	3,991	1,105,408	Clustering of lymphoid neoplasms by cell of origin, somatic mutation and drug usage profiles: a multi-trait genome-wide association study.
GCST010508	Clay-Gilmour AI	2020	2,434	2,705	Coinherited genetics of multiple myeloma and its precursor, monoclonal gammopathy of undetermined significance.
GCST002140	Chubb D	2013	2,335	7,306	Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	4
Tier 2: splice/UTR	2
Tier 3: regulatory	1
Tier 4: intronic/intergenic	43

MAF distribution

Bucket	Variants
common (>=0.05)	46
low_freq (0.01-0.05)	0
rare (<0.01)	3
unknown	1

Functional consequences

Consequence	Count
intron_variant	35
intergenic_variant	6
missense_variant	4
non_coding_transcript_exon_variant	2
3_prime_UTR_variant	1
regulatory_region_variant	1
splice_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs75341503	7	21897080	A>C	0.353	intron_variant	DNAH11	1e-35	Tier 4: intronic/intergenic
rs5995688	22	39152022	A>G	0.438	intron_variant	CBX7	3e-31	Tier 4: intronic/intergenic
rs7577599	2	25390277	T>C	0.236	intron_variant	DTNB	8e-28	Tier 4: intronic/intergenic
rs139402	22	39150140	T>C	0.05	intron_variant	CBX7	5e-26	Tier 4: intronic/intergenic
rs34562254	17	16939677	G>A	0.106	missense_variant	TNFRSF13B	3e-23	Tier 1: coding
rs3132535	6	31148749	A>G,T	0.264	intron_variant	CCHCR1	2e-22	Tier 4: intronic/intergenic
rs6546615	2	25925864	C>G	0.33	intergenic_variant	NDUFB4P4 - KIF3C	7e-22	Tier 4: intronic/intergenic
rs9856633	3	41972358	A>G	0.191	intergenic_variant	ULK4 - GEMIN2P2	2e-20	Tier 4: intronic/intergenic
rs4273077	17	16945825	A>C,G,T	0.05	intron_variant	TNFRSF13B	2e-19	Tier 4: intronic/intergenic
rs10233479	7	151235958	C>T	0.09	intron_variant	CHPF2	5e-19	Tier 4: intronic/intergenic
rs6599192	3	41950916	G>A	0.05	intron_variant	ULK4	9e-18	Tier 4: intronic/intergenic
rs7621631	3	169794357	C>A,T	0.244	intron_variant	LRRC34	9e-18	Tier 4: intronic/intergenic
rs4538746	6	32664336	C>A,G,T	0.05	intron_variant	HLA-DQB1	2e-17	Tier 4: intronic/intergenic
rs9386514	6	106189027	T>C	0.192	intron_variant	ATG5	2e-16	Tier 4: intronic/intergenic
rs3731222	9	21983915	T>C	0.148	intron_variant	CDKN2A	3e-16	Tier 4: intronic/intergenic
rs877529	22	39146287	G>A,C,T	0.49	intron_variant	CBX7	8e-16	Tier 4: intronic/intergenic
rs1948915	8	127210176	T>A,C	0.328	intron_variant	CASC19, PCAT1	2e-15	Tier 4: intronic/intergenic
rs4487645	7	21898622	C>A,G,T	0.34	intron_variant	DNAH11	5e-15	Tier 4: intronic/intergenic
rs10936600	3	169796797	A>C,T	0.05	missense_variant	LRRC34	6e-15	Tier 1: coding
rs9372120	6	106219660	T>G	0.218	intron_variant	ATG5	9e-15	Tier 4: intronic/intergenic
rs79502	22	39131578	C>A,G,T	0.05	3_prime_UTR_variant	CBX7	2e-14	Tier 2: splice/UTR
rs12711846	2	111098716	A>G	0.05	non_coding_transcript_exon_variant	ACOXL, MIR4435-2HG, ACOXL-AS1	3e-14	Tier 4: intronic/intergenic
rs4525246	11	123524538	G>A,C,T	0.05	intron_variant	GRAMD1B	3e-14	Tier 4: intronic/intergenic
rs544095130	5	95896279	A>T		intron_variant	ELL2	4e-14	Tier 4: intronic/intergenic
rs10936599	3	169774313	C>G,T	0.2	missense_variant	MYNN	9e-14	Tier 1: coding
rs6066835	20	48738472	T>C	0.083	intron_variant	PREX1	1e-13	Tier 4: intronic/intergenic
rs13338946	16	30689537	T>C,G	0.26	intergenic_variant	RNU6-416P - SRCAP	1e-13	Tier 4: intronic/intergenic
rs1716981	3	41921170	G>A,C,T	0.05	intron_variant	ULK4	1e-13	Tier 4: intronic/intergenic
rs2811710	9	21991924	C>A,T	0.343	intron_variant	CDKN2A	2e-13	Tier 4: intronic/intergenic
rs11085015	19	3369574	T>G	0.173	intron_variant	NFIC	2e-13	Tier 4: intronic/intergenic

ClinVar germline variants

90 retrieved; paginated sample, class counts are floors:

39 likely pathogenic, 19 uncertain significance, 13 pathogenic, 12 pathogenic/likely pathogenic, 6 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
37922	NM_000059.4(BRCA2):c.476-1G>A	BRCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16331	NM_000142.5(FGFR3):c.1948A>G (p.Lys650Glu)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
16332	NM_000142.5(FGFR3):c.742C>T (p.Arg248Cys)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
16343	t(4;14)(p16.3;q32.3)	FGFR3	Pathogenic	no assertion criteria provided
372805	NM_003482.4(KMT2D):c.12844C>T (p.Arg4282Ter)	KMT2D	Pathogenic	criteria provided, multiple submitters, no conflicts
375963	NM_033360.4(KRAS):c.436G>C (p.Ala146Pro)	KRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
45116	NM_004985.5(KRAS):c.182A>T (p.Gln61Leu)	KRAS	Pathogenic	criteria provided, single submitter
45122	NM_004985.5(KRAS):c.35G>C (p.Gly12Ala)	KRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076150	NM_206937.2(LIG4):c.1746_1750del (p.Glu582fs)	LIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1370122	NM_206937.2(LIG4):c.597_600del (p.Gln200fs)	LIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1423545	NM_206937.2(LIG4):c.724_725del (p.Leu242fs)	LIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2736056	NM_206937.2(LIG4):c.833G>T (p.Arg278Leu)	LIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
2753565	NM_206937.2(LIG4):c.2585_2586del (p.His862fs)	LIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
279838	NM_206937.2(LIG4):c.1271_1275del (p.Lys424fs)	LIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
2852759	NM_206937.2(LIG4):c.877C>T (p.Arg293Ter)	LIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
418659	NM_206937.2(LIG4):c.1904del (p.Lys635fs)	LIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
433156	NM_206937.2(LIG4):c.1512_1513del (p.Arg505fs)	LIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
505512	NM_206937.2(LIG4):c.879_883del (p.Asn294fs)	LIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
521262	NM_206937.2(LIG4):c.613del (p.Ser205fs)	LIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
7672	NM_206937.2(LIG4):c.1738C>T (p.Arg580Ter)	LIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7673	NM_206937.2(LIG4):c.2440C>T (p.Arg814Ter)	LIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12356	NM_000546.6(TP53):c.743G>A (p.Arg248Gln)	TP53	Pathogenic	reviewed by expert panel
12366	NM_000546.6(TP53):c.818G>A (p.Arg273His)	TP53	Pathogenic	reviewed by expert panel
182957	NM_000546.6(TP53):c.216dup (p.Val73fs)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
43594	NM_000546.6(TP53):c.817C>T (p.Arg273Cys)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
800352	NM_002892.4(ARID4A):c.2614G>T (p.Glu872Ter)	ARID4A	Likely pathogenic	no assertion criteria provided
800343	NM_000051.4(ATM):c.5005G>A (p.Glu1669Lys)	ATM	Likely pathogenic	no assertion criteria provided
800338	NM_198437.3(AURKA):c.1038C>A (p.Phe346Leu)	AURKA	Likely pathogenic	no assertion criteria provided
800323	NM_004656.4(BAP1):c.1787G>C (p.Ser596Thr)	BAP1	Likely pathogenic	no assertion criteria provided
800344	NM_000465.4(BARD1):c.1946_1966del (p.Glu649_Glu655del)	BARD1	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 154 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 2

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
CCND1	CCND1	GWAS, Orphanet
CDKN2A	CDKN2A	GWAS, Orphanet

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
CCND1	Act	HNSC,PCM,UCEC	CIViC #8
BRAF	Act	BLCA,BRCA,CHOL,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,GBM,GIST,HGGNOS,LGGNOS,LUAD,MEL,MLYM,NSCLC,OVT,PAST,PCM,PRAD,PRCC,PROSTATE,READ,SACA,SKCM,STAD,UCEC,WDTC	CIViC #5
CRBN			CIViC #11761
FGFR3	Act	BLADDER,BLCA,HNSC,LUSC,PCM,PLMESO,UTUC	CIViC #23
KRAS	Act	ALL,AML,ANSC,BLADDER,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,HCC,LUAD,LUSC,MEL,MGCT,MT,NSCLC,OVT,PAAD,PANCREAS,PAST,PCM,PRAD,PRCC,READ,STAD,STOMACH,UCEC,UCS,WDTC	CIViC #30
CTAG1B			CIViC #1278
CTAG2			CIViC #11492
MYC	Act	AML,BL,MLYM,NHL	CIViC #3737
MYCL			CIViC #3738
NRAS	Act	ALL,AML,ANGS,CHOL,CLLSLL,COAD,COADREAD,GBM,HCC,LGGNOS,LUAD,LUSC,MEL,MGCT,NPC,OVT,PCM,PROSTATE,SKCM,THYM,UCEC,WDTC	CIViC #36
RXRA	Act	BLCA
SGK1	Act	DLBCLNOS,MLYM,NHL,PRCC	CIViC #5225
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
KDM5C	LoF	CCRCC,HNSC,LUAD,OVT,PAAD,PCM,RCC	CIViC #6538
AURKA			CIViC #61
TCF19			CIViC #5654
TCF3			CIViC #5646
NKX2-1	LoF	LGGNOS	CIViC #80
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45
KMT2C	LoF	ACC,ACYC,AML,ANSC,BCC,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,ES,ESCA,GBC,HCC,HNSC,LUAD,LUSC,MBL,MEL,NPC,OVT,PAAD,PANCREAS,PANET,PAST,PGNG,PRAD,PRCC,PROSTATE,RCC,SACA,SCLC,STAD,STOMACH,UCEC,WDTC	CIViC #14089
MGA	LoF	CLLSLL,LUAD,PLMESO,PRAD	CIViC #9427
HDAC4	Act	THYM
P2RY8	Act	BL,DLBCLNOS,MLYM,NHL	CIViC #21634
SAMHD1	LoF	PCM
YAP1			CIViC #8292
CDKN2A	LoF	ACYC,BLCA,BRCA,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,GBM,HCC,HNSC,LGGNOS,LUAD,LUSC,MEL,MLYM,NPC,NSCLC,OS,PAAD,PANCREAS,RCC,SKCM,SKIN,STAD,STOMACH,WDTC	CIViC #14
CDKN2C	Act	BL,HGGNOS,LGGNOS
DIS3	Act	PCM
CREBBP	LoF	ALL,BCC,BLADDER,BLCA,BRCA,CCRCC,CLLSLL,DLBCLNOS,ESCA,HCC,HNSC,LUSC,MBL,MLYM,NETNOS,NHL,NSCLC,OVT,PANCREAS,PAST,SACA,SCLC,UTUC,VULVA,WDTC	CIViC #1193
ASXL2	LoF	AML,BLCA

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CCND1	Orphanet:29073	Multiple myeloma
CCND1	Orphanet:52416	Mantle cell lymphoma
CCND1	Orphanet:67038	B-cell chronic lymphocytic leukemia
CCND1	Orphanet:892	Von Hippel-Lindau disease
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
CRBN	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
FGFR3	Orphanet:15	Achondroplasia
FGFR3	Orphanet:1860	Thanatophoric dysplasia type 1
FGFR3	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR3	Orphanet:251576	Gliosarcoma
FGFR3	Orphanet:251579	Giant cell glioblastoma
FGFR3	Orphanet:35099	Non-syndromic bicoronal craniosynostosis
FGFR3	Orphanet:429	Hypochondroplasia
FGFR3	Orphanet:53271	Muenke syndrome
FGFR3	Orphanet:794	Saethre-Chotzen syndrome
FGFR3	Orphanet:85164	Camptodactyly-tall stature-scoliosis-hearing loss syndrome
FGFR3	Orphanet:85165	Severe achondroplasia-developmental delay-acanthosis nigricans syndrome
FGFR3	Orphanet:93262	Crouzon syndrome-acanthosis nigricans syndrome
FGFR3	Orphanet:93274	Thanatophoric dysplasia type 2
KRAS	Orphanet:1333	Familial pancreatic carcinoma
KRAS	Orphanet:1340	Cardiofaciocutaneous syndrome
KRAS	Orphanet:144	Lynch syndrome
KRAS	Orphanet:146	Differentiated thyroid carcinoma
KRAS	Orphanet:2396	Encephalocraniocutaneous lipomatosis
KRAS	Orphanet:251615	Pilomyxoid astrocytoma
KRAS	Orphanet:2612	Linear nevus sebaceus syndrome
KRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
KRAS	Orphanet:3339	Oculoectodermal syndrome
KRAS	Orphanet:648	Noonan syndrome
KRAS	Orphanet:86834	Juvenile myelomonocytic leukemia
MYC	Orphanet:480541	High grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement
MYC	Orphanet:543	Burkitt lymphoma
MYC	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
NRAS	Orphanet:146	Differentiated thyroid carcinoma
NRAS	Orphanet:2612	Linear nevus sebaceus syndrome
NRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
NRAS	Orphanet:389	Langerhans cell histiocytosis
NRAS	Orphanet:626	Large/giant congenital melanocytic nevus
NRAS	Orphanet:648	Noonan syndrome
NRAS	Orphanet:86834	Juvenile myelomonocytic leukemia

Cohort genes → proteins

75 cohort genes, 72 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	33
civic_only	5
multi_evidence	37

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CCND1	HGNC:1582	ENSG00000110092	P24385	G1/S-specific cyclin-D1	gwas,clinvar,civic_evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	clinvar,civic_evidence
CRBN	HGNC:30185	ENSG00000113851	Q96SW2	Protein cereblon	clinvar,civic_evidence
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	clinvar,civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar,civic_evidence
CTAG1B	HGNC:2491	ENSG00000184033	P78358	Cancer/testis antigen 1	civic_evidence
CTAG2	HGNC:2492	ENSG00000126890	O75638	Cancer/testis antigen 2	civic_evidence
MYC	HGNC:7553	ENSG00000136997	P01106	Myc proto-oncogene protein	civic_evidence
MYCL	HGNC:7555	ENSG00000116990	P12524	Protein L-Myc	civic_evidence
NRAS	HGNC:7989	ENSG00000213281	P01111	GTPase NRas	civic_evidence
RXRA	HGNC:10477	ENSG00000186350	P19793	Retinoic acid receptor RXR-alpha	clinvar
SGK1	HGNC:10810	ENSG00000118515	O00141	Serine/threonine-protein kinase Sgk1	clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
SMARCD3	HGNC:11108	ENSG00000082014	Q6STE5	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 3	gwas
KDM5C	HGNC:11114	ENSG00000126012	P41229	Lysine-specific demethylase 5C	clinvar
AURKA	HGNC:11393	ENSG00000087586	O14965	Aurora kinase A	clinvar
TCF19	HGNC:11629	ENSG00000137310	Q9Y242	Transcription factor 19	gwas
TCF3	HGNC:11633	ENSG00000071564	P15923	Transcription factor E2-alpha	clinvar
TCF7L1	HGNC:11640	ENSG00000152284	Q9HCS4	Transcription factor 7-like 1	clinvar
TERC	HGNC:11727	ENSG00000270141		telomerase RNA component	gwas
NKX2-1	HGNC:11825	ENSG00000136352	P43699	Homeobox protein Nkx-2.1	clinvar
TOM1	HGNC:11982	ENSG00000100284	O60784	Target of Myb1 membrane trafficking protein	gwas
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
TRAF5	HGNC:12035	ENSG00000082512	O00463	TNF receptor-associated factor 5	clinvar
KMT2C	HGNC:13726	ENSG00000055609	Q8NEZ4	Histone-lysine N-methyltransferase 2C	clinvar
CCHCR1	HGNC:13930	ENSG00000204536	Q8TD31	Coiled-coil alpha-helical rod protein 1	gwas
MGA	HGNC:14010	ENSG00000174197	Q8IWI9	MAX gene-associated protein	clinvar
HDAC4	HGNC:14063	ENSG00000068024	P56524	Histone deacetylase 4	clinvar
MYNN	HGNC:14955	ENSG00000085274	Q9NPC7	Myoneurin	gwas
P2RY8	HGNC:15524	ENSG00000182162	Q86VZ1	S-geranylgeranyl-glutathione receptor P2RY8	clinvar
CBX7	HGNC:1557	ENSG00000100307	O95931	Chromobox protein homolog 7	gwas
ULK4	HGNC:15784	ENSG00000168038	Q96C45	Serine/threonine-protein kinase ULK4	gwas
SAMHD1	HGNC:15925	ENSG00000101347	Q9Y3Z3	Deoxynucleoside triphosphate triphosphohydrolase SAMHD1	clinvar
YAP1	HGNC:16262	ENSG00000137693	P46937	Transcriptional coactivator YAP1	clinvar
SRCAP	HGNC:16974	ENSG00000080603	Q6ZRS2	Chromatin remodeling protein SRCAP	gwas
ELL2	HGNC:17064	ENSG00000118985	O00472	RNA polymerase II elongation factor ELL2	gwas
PSORS1C2	HGNC:17199	ENSG00000204538	Q9UIG4	Psoriasis susceptibility 1 candidate gene 2 protein	gwas
PSORS1C1	HGNC:17202	ENSG00000204540	Q9UIG5	Psoriasis susceptibility 1 candidate gene 1 protein	gwas
WAC	HGNC:17327	ENSG00000095787	Q9BTA9	WW domain-containing adapter protein with coiled-coil	gwas
DTNBP1	HGNC:17328	ENSG00000047579	Q96EV8	Dysbindin	gwas
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	gwas
CDKN2C	HGNC:1789	ENSG00000123080	P42773	Cyclin-dependent kinase 4 inhibitor C	clinvar
CDSN	HGNC:1802	ENSG00000204539	Q15517	Corneodesmosin	gwas
TNFRSF13B	HGNC:18153	ENSG00000240505	O14836	Tumor necrosis factor receptor superfamily member 13B	gwas
DIS3	HGNC:20604	ENSG00000083520	Q9Y2L1	Exosome complex exonuclease RRP44	clinvar
CREBBP	HGNC:2348	ENSG00000005339	Q92793	CREB-binding protein	clinvar
ASXL2	HGNC:23805	ENSG00000143970	Q76L83	Putative Polycomb group protein ASXL2	gwas
ACTRT3	HGNC:24022	ENSG00000184378	Q9BYD9	Actin-related protein T3	gwas
BMF	HGNC:24132	ENSG00000104081	Q96LC9	Bcl-2-modifying factor	gwas
NCAPH2	HGNC:25071	ENSG00000025770	Q6IBW4	Condensin-2 complex subunit H2	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CCND1	G1/S-specific cyclin-D1	Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
CRBN	Protein cereblon	Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2, ILF2 or GLUL.
FGFR3	Fibroblast growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
MYC	Myc proto-oncogene protein	Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5’-CAC[GA]TG-3'.
NRAS	GTPase NRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
RXRA	Retinoic acid receptor RXR-alpha	Receptor for retinoic acid that acts as a transcription factor.
SGK1	Serine/threonine-protein kinase Sgk1	Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration a…
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
SMARCD3	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 3	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
KDM5C	Lysine-specific demethylase 5C	Histone demethylase that specifically demethylates ‘Lys-4’ of histone H3, thereby playing a central role in histone code.
AURKA	Aurora kinase A	Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression.
TCF19	Transcription factor 19	Potential transcription factor that may play a role in the regulation of genes involved in cell cycle G1/S transition.
TCF3	Transcription factor E2-alpha	Transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition.
TCF7L1	Transcription factor 7-like 1	Participates in the Wnt signaling pathway.
NKX2-1	Homeobox protein Nkx-2.1	Transcription factor that binds and activates the promoter of thyroid specific genes such as thyroglobulin, thyroperoxidase, and thyrotropin receptor.
TOM1	Target of Myb1 membrane trafficking protein	Adapter protein that plays a role in the intracellular membrane trafficking of ubiquitinated proteins, thereby participating in autophagy, ubiquitination-dependent signaling and receptor recycling pathways.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
TRAF5	TNF receptor-associated factor 5	Adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases.
KMT2C	Histone-lysine N-methyltransferase 2C	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).
CCHCR1	Coiled-coil alpha-helical rod protein 1	May be a regulator of keratinocyte proliferation or differentiation.
MGA	MAX gene-associated protein	Functions as a dual-specificity transcription factor, regulating the expression of both MAX-network and T-box family target genes.
HDAC4	Histone deacetylase 4	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
P2RY8	S-geranylgeranyl-glutathione receptor P2RY8	G protein-coupled receptor for S-geranylgeranyl-glutathione (GGG), an endogenous metabolite present in lymphoid tissues.
CBX7	Chromobox protein homolog 7	Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.
ULK4	Serine/threonine-protein kinase ULK4	May be involved in the remodeling of cytoskeletal components, such as alpha-tubulin, and in this way regulates neurite branching and elongation, as well as cell motility.
SAMHD1	Deoxynucleoside triphosphate triphosphohydrolase SAMHD1	Protein that acts both as a host restriction factor involved in defense response to virus and as a regulator of DNA end resection at stalled replication forks.
YAP1	Transcriptional coactivator YAP1	Transcriptional regulator with dual roles as a coactivator and corepressor.
SRCAP	Chromatin remodeling protein SRCAP	Acts both as a chromatin remodeler and transcription coregulator.
ELL2	RNA polymerase II elongation factor ELL2	Elongation factor component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA.
WAC	WW domain-containing adapter protein with coiled-coil	Acts as a linker between gene transcription and histone H2B monoubiquitination at ‘Lys-120’ (H2BK120ub1).
DTNBP1	Dysbindin	Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
CDKN2C	Cyclin-dependent kinase 4 inhibitor C	Interacts strongly with CDK6, weakly with CDK4.
CDSN	Corneodesmosin	Important for the epidermal barrier integrity.
TNFRSF13B	Tumor necrosis factor receptor superfamily member 13B	Receptor for TNFSF13/APRIL and TNFSF13B/TALL1/BAFF/BLYS that binds both ligands with similar high affinity.
DIS3	Exosome complex exonuclease RRP44	Putative catalytic component of the RNA exosome complex which has 3’->5’ exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events.
CREBBP	CREB-binding protein	Acetylates histones, giving a specific tag for transcriptional activation.
ASXL2	Putative Polycomb group protein ASXL2	Putative Polycomb group (PcG) protein.
BMF	Bcl-2-modifying factor	May play a role in apoptosis.
NCAPH2	Condensin-2 complex subunit H2	Regulatory subunit of the condensin-2 complex, a complex that seems to provide chromosomes with an additional level of organization and rigidity and in establishing mitotic chromosome architecture.
RFWD3	E3 ubiquitin-protein ligase RFWD3	E3 ubiquitin-protein ligase required for the repair of DNA interstrand cross-links (ICL) in response to DNA damage.
BCORL1	BCL-6 corepressor-like protein 1	Transcriptional corepressor.
TET2	Methylcytosine dioxygenase TET2	Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation.
CEP20	Centrosomal protein 20	Involved in the biogenesis of cilia.
TET3	Methylcytosine dioxygenase TET3	Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming in the zygote following fertilization.
LRRC34	Leucine-rich repeat-containing protein 34	Highly expressed in stem cells where it may be involved in regulation of pluripotency.
PRR14	Proline-rich protein 14	Functions in tethering peripheral heterochromatin to the nuclear lamina during interphase, possibly through the interaction with heterochromatin protein CBX5/HP1 alpha.
GRAMD1B	Protein Aster-B	Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER).

Protein-family classification

Druggable: 12 · Difficult: 25 · Unknown: 38 · Druggable fraction: 0.16

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
Transcription factor	18	2.0×	0.025
Kinase	6	2.2×	0.214
Nuclear receptor	1	5.2×	0.354
Scaffold/PPI	7	1.6×	0.354
Complement	1	3.6×	0.392
Other/Unknown	38	0.9×	0.960
Enzyme (other)	3	0.5×	0.960
GPCR	1	0.3×	0.960

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CCND1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
CRBN	Other/Unknown	no		Lon_prtase_N, Yippee/Mis18/Cereblon, PUA-like_sf
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
CTAG1B	Other/Unknown	no		CTAG/Pcc1
CTAG2	Other/Unknown	no		CTAG/Pcc1
MYC	Transcription factor	no		Tscrpt_reg_Myc, Myc-LZ, bHLH_dom
MYCL	Transcription factor	no		Tscrpt_reg_Myc, bHLH_dom, Tscrpt_reg_Myc_N
NRAS	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
RXRA	Nuclear receptor	yes		Retinoid-X_rcpt/HNF4, Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt
SGK1	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
SMARCD3	Other/Unknown	no		SWIB_MDM2_domain, SWIB_domain, SWIB_MDM2_dom_sf
KDM5C	Transcription factor	no	1.14.11.67	ARID_dom, Znf_PHD, JmjC_dom
AURKA	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TCF19	Transcription factor	no		FHA_dom, Znf_PHD, SMAD_FHA_dom_sf
TCF3	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, NeuroDiff_E-box_TFs
TCF7L1	Other/Unknown	no		HMG_box_dom, CTNNB1-bd_N, TCF/LEF
TERC	Other/Unknown	no
NKX2-1	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
TOM1	Other/Unknown	no		VHS_dom, GAT_dom, ENTH_VHS
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
TRAF5	Transcription factor	no		Znf_TRAF, Znf_RING, MATH/TRAF_dom
KMT2C	Transcription factor	no		HMGI/Y_DNA-bd_CS, SET_dom, Znf_RING
CCHCR1	Other/Unknown	no		HCR
MGA	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, bHLH_dom
HDAC4	Enzyme (other)	yes	3.5.1.98	HDACs, Ureohydrolase_dom_sf, His_deacetylse_dom
MYNN	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
P2RY8	GPCR	yes		GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, P2Y8_rcpt
CBX7	Other/Unknown	no		Chromo/chromo_shadow_dom, Chromo-like_dom_sf, Chromo_dom_subgr
ULK4	Kinase	yes		Prot_kinase_dom, Kinase-like_dom_sf, ARM-like
SAMHD1	Transcription factor	no	3.1.5.B1	SAM, HD/PDEase_dom, HD_domain
YAP1	Scaffold/PPI	no		WW_dom, WW_dom_sf, YAP1
SRCAP	Other/Unknown	no		SNF2_N, Helicase_C-like, Helicase_ATP-bd
ELL2	Other/Unknown	no		Occludin_ELL, ELL_N, ELL/occludin
PSORS1C2	Other/Unknown	no		SPR1
PSORS1C1	Other/Unknown	no		SEEK1
WAC	Scaffold/PPI	no		WW_dom, WW_dom_sf, WAC
DTNBP1	Other/Unknown	no		Dysbindin
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
CDKN2C	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor
CDSN	Other/Unknown	no		Corneodesmosin
TNFRSF13B	Other/Unknown	no		TACI_Cys-rich-dom, TNFR_13B
DIS3	Other/Unknown	no		RNase_II/R, PIN_dom, NA-bd_OB-fold
CREBBP	Transcription factor	no	2.3.1.48	Znf_TAZ, Znf_ZZ, Bromodomain
ASXL2	Other/Unknown	no		Asxl_HARE-HTH, ASX/ASX-like, ASX-like_PHD
ACTRT3	Other/Unknown	no		Actin, Actin/actin-like_CS, ATPase_NBD
BMF	Other/Unknown	no		BMF
NCAPH2	Other/Unknown	no		H2_N, H2_M, CNDH2_C

Expression context

Cohort genes with no expression data: 1.

66 cohort genes 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)	74
unknown	1

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	9
secondary oocyte	8
male germ line stem cell (sensu Vertebrata) in testis	7
primordial germ cell in gonad	6
sural nerve	6
calcaneal tendon	5
ganglionic eminence	5
oocyte	5
stromal cell of endometrium	4
buccal mucosa cell	4
tendon of biceps brachii	4
monocyte	4
bone marrow cell	4
upper arm skin	3
skin of hip	3
upper leg skin	3
testis	3
leukocyte	3
mononuclear cell	3
right hemisphere of cerebellum	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CCND1	280	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, upper arm skin
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
CRBN	288	ubiquitous	marker	calcaneal tendon, Brodmann (1909) area 23, skin of hip
FGFR3	262	broad	marker	upper leg skin, skin of hip, upper arm skin
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
CTAG1B	36	tissue_specific	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, testis
CTAG2	132		yes	tendon of biceps brachii, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
MYC	256	ubiquitous	marker	upper leg skin, vena cava, left uterine tube
MYCL	201	broad	marker	monocyte, mononuclear cell, leukocyte
NRAS	278	ubiquitous	marker	gingival epithelium, epithelium of nasopharynx, secondary oocyte
RXRA	294	ubiquitous	marker	skin of hip, gingival epithelium, pancreatic ductal cell
SGK1	299	ubiquitous	marker	palpebral conjunctiva, eye, right lung
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
SMARCD3	280	ubiquitous	marker	ganglionic eminence, nucleus accumbens, right hemisphere of cerebellum
KDM5C	279	ubiquitous	marker	sural nerve, stromal cell of endometrium, right uterine tube
AURKA	236	ubiquitous	marker	oocyte, secondary oocyte, ventricular zone
TCF19	133	ubiquitous	yes	primordial germ cell in gonad, ventricular zone, lymph node
TCF3	294	ubiquitous	marker	ganglionic eminence, ventricular zone, embryo
TCF7L1	230	ubiquitous	marker	popliteal artery, tibial artery, aorta
TERC	113	ubiquitous	yes	bone marrow cell, colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis
NKX2-1	101	broad	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
TOM1	207	ubiquitous	marker	lower esophagus mucosa, gastrocnemius, muscle of leg
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
TRAF5	256	ubiquitous	marker	saphenous vein, body of pancreas, blood vessel layer
KMT2C	261	ubiquitous	marker	oocyte, caput epididymis, upper arm skin
CCHCR1	134	ubiquitous	marker	left testis, right testis, testis
MGA	279	ubiquitous	marker	calcaneal tendon, oocyte, tendon
HDAC4	277	ubiquitous	marker	sural nerve, gluteal muscle, gastrocnemius
MYNN	274	ubiquitous	marker	buccal mucosa cell, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis
P2RY8	167		marker	buccal mucosa cell, granulocyte, blood

Protein interactions among cohort

Intra-cohort edges: 71.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
MYC	20,608
KRAS	14,509
CDKN2A	9,311
CCND1	8,328
NRAS	7,598
BRAF	7,394
CREBBP	6,959
YAP1	6,742
AURKA	6,376

Intra-cohort edges

A	B	Sources
ACTRT3	LRRC34	string_interaction
ACTRT3	MYNN	string_interaction
AURKA	MYC	string_interaction
AURKA	TP53	string_interaction
BCORL1	HDAC4	string_interaction
BMF	CTAG1B	biogrid_interaction
BRAF	BRCA2	biogrid_interaction
BRAF	CDKN2A	string_interaction
BRAF	EIF1AX	string_interaction
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	MYCL	intact
BRAF	NRAS	biogrid_interaction, intact, string_interaction
BRAF	TP53	string_interaction
BRCA2	CCND1	intact
BRCA2	TP53	string_interaction
CBX7	CDKN2A	string_interaction
CCHCR1	CDSN	string_interaction
CCHCR1	PSORS1C1	string_interaction
CCHCR1	PSORS1C2	string_interaction
CCHCR1	TCF19	string_interaction
CCND1	CDKN2A	biogrid_interaction, string_interaction
CCND1	CDKN2C	string_interaction
CCND1	MYC	string_interaction
CCND1	TCF7L1	string_interaction
CCND1	TP53	string_interaction
CDCA7L	DNAH11	string_interaction
CDCA7L	MYC	string_interaction
CDCA7L	PRR14	string_interaction
CDCA7L	ULK4	string_interaction
CDKN2A	KRAS	string_interaction
CDKN2A	MYC	string_interaction
CDKN2A	TOM1	string_interaction
CDKN2A	TP53	string_interaction
CDKN2C	TP53	string_interaction
CDSN	PSORS1C1	string_interaction
CDSN	PSORS1C2	string_interaction
CDSN	TCF19	string_interaction
CREBBP	MYC	biogrid_interaction
CREBBP	SRCAP	string_interaction
CREBBP	TCF3	biogrid_interaction
CREBBP	TP53	biogrid_interaction, intact, string_interaction
DNMT3A	FLT3	string_interaction
DNMT3A	MYC	biogrid_interaction, string_interaction
DNMT3A	TET2	string_interaction
DNMT3A	TET3	string_interaction
DTNB	DTNBP1	biogrid_interaction, string_interaction
EIF1AX	NRAS	string_interaction
ELL2	FGFR3	intact
FAT1	KRAS	string_interaction
FAT1	TP53	string_interaction

Structural data

PDB: 51 · AlphaFold-only: 22 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
TP53	P04637	313
AURKA	O14965	193
CREBBP	Q92793	144
BRAF	P15056	131
RXRA	P19793	110
CRBN	Q96SW2	90
SAMHD1	Q9Y3Z3	76
H2AC16	P0C0S8	65
H2AC17	P0C0S8	65
DNMT3A	Q9Y6K1	43
YAP1	P46937	41
NRAS	P01111	35
ETF1	P62495	33
EIF1AX	P47813	29
H1-4	P10412	26
MYC	P01106	25
CTAG1B	P78358	23
HDAC4	P56524	19
FGFR3	P22607	15
BRCA2	P51587	14
PREX1	Q8TCU6	14
CCND1	P24385	11
FLT3	P36888	11
SRCAP	Q6ZRS2	10
KMT2C	Q8NEZ4	9
CBX7	O95931	8
TOM1	O60784	6
CDKN2C	P42773	6
TET2	Q6N021	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACTRT3	Q9BYD9	94.47
CHPF2	Q9P2E5	84.86
SMARCD3	Q6STE5	80.99
CCHCR1	Q8TD31	79.52
DTNB	O60941	76.29
DTNBP1	Q96EV8	75.92
CEP20	Q96NB1	73.95
PSORS1C2	Q9UIG4	71.08
GRAMD1B	Q3KR37	68.76
MYCL	P12524	64.82
SH2B3	Q9UQQ2	63.45
TCF19	Q9Y242	63.17
EOMES	O95936	56.74
WAC	Q9BTA9	55.71
PRR14	Q9BWN1	55.62
PSORS1C1	Q9UIG5	55.10
TCF7L1	Q9HCS4	52.59
CTAG2	O75638	47.90
CDSN	Q15517	38.13
MGA	Q8IWI9
DNAH11	Q96DT5
FAT1	Q14517

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 690. Enrichment computed across 107 evidence-associated genes (77 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 77 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Gene expression (Transcription)	20	4.6×	3e-06	CCND1, RXRA, SGK1, SMARCD3, AURKA, TCF3, TCF7L1, KMT2C (+12 more)
RNA Polymerase II Transcription	17	5.0×	1e-05	CCND1, RXRA, SGK1, SMARCD3, AURKA, TCF3, TCF7L1, KMT2C (+9 more)
RUNX3 regulates p14-ARF	4	59.3×	7e-05	CCND1, KRAS, HDAC4, CDKN2A
Transcriptional regulation by RUNX3	6	21.2×	7e-05	CCND1, TCF7L1, CDKN2A, CREBBP, MYC, BCL2L11
Specification of primordial germ cells	4	45.6×	1e-04	TET2, EOMES, POU5F1, PRDM1
Cellular response to chemical stress	7	13.0×	1e-04	RXRA, SMARCD3, CDKN2A, CREBBP, ABCC1, MYC, NCOR2
Chromatin modifying enzymes	9	8.4×	1e-04	CCND1, SMARCD3, KDM5C, KMT2C, CREBBP, H3C1, KMT2D, NCOR2 (+1 more)
Epigenetic regulation of gene expression	9	8.3×	1e-04	RXRA, SMARCD3, KMT2C, CREBBP, TET2, TET3, JARID2, KMT2D (+1 more)
FLT3 Signaling	5	22.5×	2e-04	KRAS, SH2B3, FLT3, NRAS, BCL2L11
Chromatin organization	8	8.5×	3e-04	CCND1, SMARCD3, KDM5C, KMT2C, CREBBP, KMT2D, NCOR2, ARID4A
Generic Transcription Pathway	17	3.3×	5e-04	CCND1, RXRA, SGK1, SMARCD3, AURKA, TCF3, TCF7L1, KMT2C (+9 more)
RAS signaling downstream of NF1 loss-of-function variants	3	63.6×	6e-04	KRAS, NF1, NRAS
RMTs methylate histone arginines	6	11.4×	7e-04	CCND1, SMARCD3, DNMT3A, H2AC16, H2AC17, H3C1
Transcriptional regulation by RUNX1	6	11.4×	7e-04	CCND1, SMARCD3, TCF3, KMT2C, CREBBP, KMT2D
Activation of HOX genes during differentiation	4	22.8×	0.001	RXRA, KMT2C, CREBBP, KMT2D
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	5	14.0×	0.001	RXRA, KMT2C, CREBBP, KMT2D, NCOR2
RUNX3 regulates WNT signaling	3	44.5×	0.001	CCND1, TCF7L1, MYC
Regulation of TP53 Expression	2	148.3×	0.002	TP53, PRDM1
Downstream signal transduction	4	19.8×	0.002	KRAS, NCK1, NRAS, PIK3R2
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	5	12.8×	0.002	RXRA, KMT2C, CREBBP, KMT2D, NCOR2
Cellular responses to stress	10	4.8×	0.002	RXRA, SMARCD3, CDKN2A, CDKN2C, DIS3, CREBBP, ABCC1, MYC (+2 more)
Defective homologous recombination repair (HRR) due to PALB2 loss of function	3	37.1×	0.002	BRCA2, ATM, BARD1
Cytoprotection by HMOX1	5	12.0×	0.002	RXRA, SMARCD3, CREBBP, ABCC1, NCOR2
MITF-M-dependent gene expression	5	11.8×	0.002	CCND1, SMARCD3, TCF7L1, CDKN2A, IRF4
MITF-M-regulated melanocyte development	6	8.9×	0.002	CCND1, SMARCD3, TCF7L1, CDKN2A, CREBBP, IRF4
Developmental Biology	16	3.0×	0.002	CCND1, RXRA, SMARCD3, TCF3, TCF7L1, KMT2C, CDKN2A, CDSN (+8 more)
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	3	34.2×	0.002	KRAS, NRAS, PIK3R2
Signaling by PDGFRA extracellular domain mutants	3	34.2×	0.002	KRAS, NRAS, PIK3R2
Oncogene Induced Senescence	4	17.4×	0.002	TP53, CDKN2A, CDKN2C, ERF
Nuclear events mediated by NFE2L2	4	17.4×	0.002	CDKN2A, CREBBP, ABCC1, MYC

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 100 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of transcription by RNA polymerase II	23	4.1×	6e-06	CCND1, RXRA, TCF3, NKX2-1, TP53, HDAC4, CBX7, YAP1 (+15 more)
positive regulation of transcription by RNA polymerase II	23	3.4×	8e-05	RXRA, TCF3, NKX2-1, TP53, KMT2C, HDAC4, YAP1, SRCAP (+15 more)
chromatin remodeling	10	7.3×	4e-04	SMARCD3, KDM5C, HDAC4, SRCAP, WAC, EOMES, IRF4, JARID2 (+2 more)
mitotic G1 DNA damage checkpoint signaling	4	42.1×	6e-04	CCND1, TP53, WAC, RFWD3
positive regulation of DNA-templated transcription	15	4.2×	6e-04	RXRA, BRCA2, SMARCD3, TCF3, NKX2-1, TP53, MGA, HDAC4 (+7 more)
response to X-ray	4	35.5×	6e-04	CCND1, BRCA2, TP53, LIG4
T cell differentiation in thymus	5	20.6×	6e-04	BRAF, TP53, NCAPH2, IL7R, LIG4
gene expression	9	7.2×	6e-04	KRAS, NKX2-1, LRRC34, EOMES, ABCC1, ABCC6, IL7R, PRDM1 (+1 more)
positive regulation of release of cytochrome c from mitochondria	4	30.6×	1e-03	TP53, BMF, BAK1, BCL2L11
positive regulation of apoptotic process	10	5.7×	0.001	TP53, CDKN2A, BMF, IRF8, LATS1, NF1, ATM, BAK1 (+2 more)
DNA damage response	10	5.3×	0.002	CCND1, SGK1, TP53, SAMHD1, YAP1, WAC, RFWD3, MYC (+2 more)
response to gamma radiation	4	23.2×	0.002	BRCA2, TP53, LIG4, BAK1
B cell homeostasis	4	22.5×	0.002	TNFRSF13B, IL7R, BAK1, BCL2L11
tissue homeostasis	4	22.5×	0.002	YAP1, ABCC1, BAP1, BARD1
thymocyte apoptotic process	3	42.1×	0.003	TP53, BAK1, BCL2L11
somatic stem cell population maintenance	5	12.4×	0.003	BRAF, YAP1, CDKN2A, LIG4, POU5F1
MAPK cascade	6	9.2×	0.003	BRAF, FGFR3, KRAS, MYC, NF1, NRAS
negative regulation of epithelial cell differentiation	3	36.1×	0.004	CCND1, KRAS, YAP1
regulation of DNA damage checkpoint	3	33.7×	0.005	BRCA2, RFWD3, BARD1
forebrain astrocyte development	2	112.3×	0.005	KRAS, NF1
cellular response to nitrosative stress	2	112.3×	0.005	ATG5, ATM
cellular response to ionizing radiation	4	16.4×	0.005	BRCA2, TP53, LIG4, BARD1
replicative senescence	3	29.7×	0.006	TP53, CDKN2A, ATM
Ras protein signal transduction	5	10.3×	0.006	KRAS, TP53, CDKN2A, NF1, NRAS
negative regulation of B cell proliferation	3	28.1×	0.007	CDKN2A, TNFRSF13B, ATM
pro-B cell differentiation	2	84.3×	0.008	FLT3, LIG4
response to fungus	2	84.3×	0.008	ATG5, BAK1
negative regulation of stem cell proliferation	3	25.3×	0.008	TP53, CDKN2C, NF1
positive regulation of protein-containing complex assembly	4	13.5×	0.008	CRBN, BMF, BAK1, BCL2L11
thymus development	4	13.5×	0.008	BRAF, JARID2, ATM, BCL2L11

Therapeutics

Drugs indicated for this disease

21 approved, 64 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Belantamab Mafodotin	Approved (phase 4)
Carfilzomib	Approved (phase 4)
Carmustine	Approved (phase 4)
Ciltacabtagene Autoleucel	Approved (phase 4)
Daratumumab	Approved (phase 4)
Dexamethasone Acetate	Approved (phase 4)
Elotuzumab	Approved (phase 4)
Elranatamab	Approved (phase 4)
INTERFERON ALFA-2B	Approved (phase 4)
Idecabtagene Vicleucel	Approved (phase 4)
Isatuximab	Approved (phase 4)
Ixazomib Citrate	Approved (phase 4)
Lenalidomide	Approved (phase 4)
Melphalan	Approved (phase 4)
Motixafortide Acetate	Approved (phase 4)
Plerixafor	Approved (phase 4)
Pomalidomide	Approved (phase 4)
Selinexor	Approved (phase 4)
Talquetamab	Approved (phase 4)
Teclistamab	Approved (phase 4)
Thalidomide	Approved (phase 4)
(R)-Melphalan	Phase 3 (in late-stage trials)
Acetaminophen	Phase 3 (in late-stage trials)
Alnuctamab	Phase 3 (in late-stage trials)
Amifostine	Phase 3 (in late-stage trials)
Amphotericin B	Phase 3 (in late-stage trials)
Anitocabtagene Autoleucel	Phase 3 (in late-stage trials)
Aprepitant	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Bendamustine	Phase 3 (in late-stage trials)
Bortezomib	Phase 3 (in late-stage trials)
Busulfan	Phase 3 (in late-stage trials)
Carvedilol	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Clarithromycin	Phase 3 (in late-stage trials)
Colchicine	Phase 3 (in late-stage trials)
Cyclosporine	Phase 3 (in late-stage trials)
Cytarabine	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Diphenhydramine	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Enalapril	Phase 3 (in late-stage trials)
Etentamig	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Felzartamab	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Fludarabine	Phase 3 (in late-stage trials)
Fludarabine Phosphate	Phase 3 (in late-stage trials)
Hyaluronidase	Phase 3 (in late-stage trials)
Hyaluronidase (Human Recombinant)	Phase 3 (in late-stage trials)
Ibandronic Acid	Phase 3 (in late-stage trials)
Iberdomide	Phase 3 (in late-stage trials)
Idarubicin	Phase 3 (in late-stage trials)
Interferon Alfa	Phase 3 (in late-stage trials)
Ixazomib	Phase 3 (in late-stage trials)
Lenograstim	Phase 3 (in late-stage trials)
Linvoseltamab	Phase 3 (in late-stage trials)
Lomustine	Phase 3 (in late-stage trials)
Masitinib	Phase 3 (in late-stage trials)
Methylprednisolone	Phase 3 (in late-stage trials)
Mezigdomide	Phase 3 (in late-stage trials)
Montelukast	Phase 3 (in late-stage trials)
Mycophenolate Mofetil	Phase 3 (in late-stage trials)
Nivolumab	Phase 3 (in late-stage trials)
Nystatin	Phase 3 (in late-stage trials)
Oblimersen Sodium	Phase 3 (in late-stage trials)
PEGINTERFERON ALFA-2B	Phase 3 (in late-stage trials)
Palifermin	Phase 3 (in late-stage trials)
Pamidronic Acid	Phase 3 (in late-stage trials)
Panobinostat	Phase 3 (in late-stage trials)
Pegfilgrastim	Phase 3 (in late-stage trials)
Pembrolizumab	Phase 3 (in late-stage trials)
Perifosine	Phase 3 (in late-stage trials)
Plitidepsin	Phase 3 (in late-stage trials)
Prednisolone	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Sargramostim	Phase 3 (in late-stage trials)
Siltuximab	Phase 3 (in late-stage trials)
Tanespimycin	Phase 3 (in late-stage trials)
Transplatin	Phase 3 (in late-stage trials)
Valspodar	Phase 3 (in late-stage trials)
Venetoclax	Phase 3 (in late-stage trials)
Vincristine	Phase 3 (in late-stage trials)
Vorinostat	Phase 3 (in late-stage trials)
Zoledronic Acid Anhydrous	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): 6-O-BENZYLGUANINE, ANTINEOPLASTON A10, Abatacept, Afatinib, Aflibercept, Aldesleukin, Allopurinol, Alvocidib, Anakinra, Arsenic Trioxide, Ascorbic Acid, Astuprotimut-R, Avelumab, Azacitidine, Balixafortide, Belinostat, Bevacizumab, Binimetinib, Budesonide, Capivasertib, Celecoxib, Cemiplimab, Cetrelimab, Cetuximab, Chloroquine, Clofarabine, Crizotinib, Curcumin, Daclizumab, Dalteparin Sodium, Dasatinib Anhydrous, Denosumab, Dinaciclib, Dovitinib, Durvalumab, Encorafenib, Enzastaurin, Epigalocatechin Gallate, Erdafitinib, Everolimus, Fenofibrate, Gemcitabine, Givinostat, Glutamine, Hydrocortisone, INDIUM IN 111 IBRITUMOMAB TIUXETAN, INTERFERON ALFA-2A, INTERFERON GAMMA-1B, Ibrutinib, Imetelstat, Inebilizumab, Ipatasertib, Isotretinoin, Keyhole Limpet Hemocyanin, Larotrectinib, Leflunomide, Lestaurtinib, Magrolimab, Marizomib, Metformin, Methotrexate, Minocycline, Motexafin Gadolinium, Motixafortide, Nelfinavir, Nirogacestat, Nogapendekin Alfa, OMEGA-3 FATTY ACIDS, Oxygen, PEGINTERFERON ALFA-2A, Paclitaxel, Palonosetron, Pasireotide, Plinabulin, Prasterone, Propranolol, Pyridoxine, Relatlimab, Rituximab, Rivaroxaban, Romidepsin, Ruxolitinib, Selumetinib, Semaxanib, Simvastatin, Sirolimus, Sonidegib, Sotatercept, TOSITUMOMAB 131I, Tabalumab, Tacedinaline, Tacrolimus Anhydrous, Tadalafil, Taselisib, Tecemotide, Temsirolimus, Tetanus Toxoid, Thiotepa, Tinzaparin, Tisagenlecleucel, Tivantinib, Tocilizumab, Topotecan, Trametinib, Trastuzumab Emtansine, Treosulfan, Tretinoin, Tucidinostat, Uproleselan, Vandetanib, Vatalanib, Vemurafenib, Vinorelbine, Vismodegib, YTTRIUM Y 90 IBRITUMOMAB TIUXETAN.

Drug target analysis

Approved (phase 4): 14 · Phase ≥3: 16 · Phased (≥1): 18 · Undrugged: 57

Druggability breadth: 49 of 107 evidence-associated genes (46%) 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
CCND1	PALBOCICLIB
BRAF	VEMURAFENIB
CRBN	DASABUVIR
FGFR3	PONATINIB
KRAS	VEMURAFENIB
RXRA	BEXAROTENE
KDM5C	DEFERIPRONE
AURKA	INAMRINONE
TP53	NITROFURANTOIN
HDAC4	CELECOXIB
CREBBP	COLCHICINE
TET2	VADADUSTAT
TET3	VADADUSTAT
FLT3	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
FLT3	143	4
AURKA	65	4
FGFR3	64	4
BRAF	48	4
CCND1	35	4
HDAC4	31	4
RXRA	23	4
CRBN	18	4
CREBBP	13	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PALBOCICLIB	4	CCND1, FLT3
ABEMACICLIB	4	BRAF, CCND1, FLT3
RIBOCICLIB	4	CCND1
TRILACICLIB	4	CCND1
VEMURAFENIB	4	BRAF, KRAS
PONATINIB	4	BRAF, CRBN, FGFR3, FLT3
FEDRATINIB	4	AURKA, BRAF, FGFR3, FLT3
SORAFENIB	4	AURKA, BRAF, FGFR3, FLT3
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF, FGFR3, FLT3
INFIGRATINIB	4	BRAF, FGFR3, FLT3
REGORAFENIB	4	BRAF, FLT3
DABRAFENIB	4	BRAF, KRAS
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF, FLT3
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	AURKA, BRAF, FGFR3, FLT3
DASATINIB	4	AURKA, BRAF, FGFR3, FLT3
ERLOTINIB	4	AURKA, BRAF, FLT3
GEFITINIB	4	BRAF, FLT3
IMATINIB	4	BRAF, FLT3
DASABUVIR	4	CRBN
POMALIDOMIDE	4	CRBN
THALIDOMIDE	4	CRBN
LENALIDOMIDE	4	CRBN
ASCIMINIB	4	CRBN
BRIGATINIB	4	AURKA, CRBN, FGFR3, FLT3
CRIZOTINIB	4	AURKA, CRBN, FGFR3, FLT3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 12.

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

Symbol	Assays	Type breakdown
CRBN	5,948	Binding:5779, Functional:154, ADMET:15
FLT3	3,132	Binding:3096, Functional:24, ADMET:8, Toxicity:4
HDAC4	1,941	Binding:1919, ADMET:13, Functional:6, Toxicity:3
AURKA	1,500	Binding:1483, Functional:10, ADMET:7
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
FGFR3	975	Binding:948, Functional:18, ADMET:9
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
RXRA	846	Binding:703, Functional:138, ADMET:5
CREBBP	687	Binding:644, Functional:43
CCND1	576	Binding:574, Functional:1, ADMET:1
SGK1	538	Binding:535, ADMET:2, Functional:1
MYC	202	Binding:202
YAP1	135	Binding:135
DNMT3A	120	Binding:118, ADMET:1, Functional:1
KDM5C	49	Binding:49
CBX7	36	Binding:35, Functional:1
KMT2C	29	Binding:29
TET2	24	Binding:24
NRAS	18	Binding:18
TET3	8	Binding:8
SAMHD1	4	Binding:3, Functional:1
MYNN	2	Binding:2
P2RY8	2	Binding:2
CDKN2A	2	Binding:2
DIS3	1	Binding:1
ETF1	1	Binding:1
H1-4	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
FGFR3	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
SGK1	2.7.11.1	non-specific serine/threonine protein kinase
KDM5C	1.14.11.67	[histone H3]-trimethyl-L-lysine4 demethylase
AURKA	2.7.11.1	non-specific serine/threonine protein kinase
HDAC4	3.5.1.98	histone deacetylase
SAMHD1	3.1.5.B1
CREBBP	2.3.1.48	histone acetyltransferase
CHPF2	2.4.1.226	N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase
DNMT3A	2.1.1.37	DNA (cytosine-5-)-methyltransferase
FLT3	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
CCND1	576
BRAF	1,442
CRBN	5,948
FGFR3	975
KRAS	861
MYC	202
RXRA	846
SGK1	538
AURKA	1,500
TP53	869
HDAC4	1,941
YAP1	135
CREBBP	687
DNMT3A	120
FLT3	3,132

Pharmacogenomics

Cohort genes with a PharmGKB record: 74; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

27 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)
PALBOCICLIB	4	CCND1, FLT3
ABEMACICLIB	4	BRAF, CCND1, FLT3
RIBOCICLIB	4	CCND1
TRILACICLIB	4	CCND1
VEMURAFENIB	4	BRAF, KRAS
PONATINIB	4	BRAF, CRBN, FGFR3, FLT3
FEDRATINIB	4	AURKA, BRAF, FGFR3, FLT3
SORAFENIB	4	AURKA, BRAF, FGFR3, FLT3
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF, FGFR3, FLT3
INFIGRATINIB	4	BRAF, FGFR3, FLT3
REGORAFENIB	4	BRAF, FLT3
DABRAFENIB	4	BRAF, KRAS
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF, FLT3
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	AURKA, BRAF, FGFR3, FLT3
DASATINIB	4	AURKA, BRAF, FGFR3, FLT3
ERLOTINIB	4	AURKA, BRAF, FLT3
GEFITINIB	4	BRAF, FLT3
IMATINIB	4	BRAF, FLT3
DASABUVIR	4	CRBN
ASCIMINIB	4	CRBN
BRIGATINIB	4	AURKA, CRBN, FGFR3, FLT3
CRIZOTINIB	4	AURKA, CRBN, FGFR3, FLT3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	14	CCND1, BRAF, CRBN, FGFR3, KRAS, RXRA, KDM5C, AURKA, TP53, HDAC4 (+4 more)
B	Phased (≥1) drug, not yet approved	4	MYC, NRAS, SGK1, CBX7
C	Druggable family + PDB, no drug	3	P2RY8, ULK4, DNMT3A
D	Druggable family + AlphaFold only, no drug	1	CHPF2
E	Difficult family or no structure, no drug	53	CTAG1B, CTAG2, MYCL, BRCA2, SMARCD3, TCF19, TCF3, TCF7L1, TERC, NKX2-1 (+43 more)

Undrugged target profiles

57 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SRCAP	0	CREBBP
SH2B3	0	TET2
CDCA7L	0	MYC
YAP1	135	—
DNMT3A	120	—
CTAG1B	0	—
CTAG2	0	—
MYCL	0	—
BRCA2	0	—
SMARCD3	0	—
TCF19	0	—
TCF3	0	—
TCF7L1	0	—
TERC	0	—
NKX2-1	0	—
TOM1	0	—
TRAF5	0	—
KMT2C	29	—
CCHCR1	0	—
MGA	0	—
MYNN	2	—
P2RY8	2	—
ULK4	0	—
SAMHD1	4	—
ELL2	0	—
PSORS1C2	0	—
PSORS1C1	0	—
WAC	0	—
DTNBP1	0	—
CDKN2A	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2,963.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	551
PHASE3	260
PHASE1/PHASE2	210
PHASE4	48
PHASE2/PHASE3	31

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03829371	PHASE4	ACTIVE_NOT_RECRUITING	STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
NCT05201781	PHASE4	RECRUITING	A Long-term Study for Participants Previously Treated With Ciltacabtagene Autoleucel
NCT05429515	PHASE4	NOT_YET_RECRUITING	Effect of HFR-SUPRA in the Treatment of Multiple Myeloma-related Acute Kidney Injury
NCT05722405	PHASE4	RECRUITING	Ixazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma
NCT05944783	PHASE4	NOT_YET_RECRUITING	Bioequivalence Studies of Dasatinib 100 Mg
NCT06057402	PHASE4	RECRUITING	Elranatamab Post Trial Access Study for Participants With Multiple Myeloma (MM)
NCT06251076	PHASE4	RECRUITING	Plan Development for Giving Teclistamab in the Outpatient Setting
NCT06409702	PHASE4	RECRUITING	Treatment of High-risk Newly Diagnosed Multiple Myeloma With Minimal Residual Disease Detection
NCT07030517	PHASE4	RECRUITING	A Study to Assess Safety of Teclistamab in Indian Participants With Relapsed and Refractory Multiple Myeloma
NCT07094048	PHASE4	RECRUITING	Immunoglobulins in Multiple Myeloma Patients Receiving a BCMA-Directed T Cell Engager
NCT07101445	PHASE4	RECRUITING	Evaluating Premedication Regimens (Methylprednisolone vs Dexamethasone-based) for the Prevention of Systemic and Injection Site Reactions to Motixafortide in Patients With Multiple Myeloma Undergoing Stem Cell Mobilization, PARADE Trial
NCT07154537	PHASE4	ACTIVE_NOT_RECRUITING	Pneumococcal Conjugated Vaccine 13 (PCV13) for Patients With Multiple Myeloma (MM)
NCT07334535	PHASE4	NOT_YET_RECRUITING	Isa-VRD in TIE HRMM
NCT07474961	PHASE4	NOT_YET_RECRUITING	BLOOD-dose: A Platform Trial Evaluating Dose Optimization in Hematological Diseases.
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00104104	PHASE4	COMPLETED	A Multiple Myeloma Trial in Patients With Bone Metastases
NCT00211211	PHASE4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00242528	PHASE4	WITHDRAWN	Open-label Study, to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Bone Lesions Secondary to Multiple Myeloma.
NCT00257114	PHASE4	COMPLETED	Evaluation of VELCADE Given as Retreatment to Multiple Myeloma Patients for Efficacy, Safety and Tolerability
NCT00352703	PHASE4	COMPLETED	PROMPT - Palifermin in Reduction of Oral Mucositis in PBSC Transplantation
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00622505	PHASE4	COMPLETED	Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants
NCT00652041	PHASE4	COMPLETED	Bortezomib/Adriamycine/Melfalan/Prednisone (VAMP)/Thalidomide/Cyclophosphamide/Dexamethasone (TaCyDex) or Bortezomib/Melfalan/Prednisone (V-MP)/TaCyDex) in Refractary or Relapsed Multiple Myeloma
NCT00733538	PHASE4	COMPLETED	Stage I Multiple Myeloma Treatment
NCT01087008	PHASE4	COMPLETED	Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse
NCT01249690	PHASE4	UNKNOWN	Efficacy Study of PAD and TAD in Newly Diagnosed Multiple Myeloma
NCT01410929	PHASE4	WITHDRAWN	Evaluation of Vertebral Compression Fracture Fixation With RF Kyphoplasty in Patients With Multiple Myeloma
NCT01731886	PHASE4	COMPLETED	Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
NCT01868828	PHASE4	UNKNOWN	A Study of PAD Versus Velcade, Cyclophosphamide and Dexamethasone (VCD) Treatment in Subjects With Multiple Myeloma
NCT02268890	PHASE4	COMPLETED	A Pharmacokinetic Study of Bortezomib in Taiwanese Participants With Multiple Myeloma
NCT02286830	PHASE4	COMPLETED	Prolonged Protection From Bone Disease in Multiple Myeloma
NCT02559154	PHASE4	UNKNOWN	Modified Bortezomib-based Combination Therapy for Multiple Myeloma
NCT02577783	PHASE4	UNKNOWN	PDD vs PAD to Treat Initially Diagnosed MM
NCT02773550	PHASE4	TERMINATED	Treatment With a Scheme With Low Doses of Bortezomib / Melphalan / Prednisone (MPV) in Patients With Multiple Myeloma
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03173092	PHASE4	TERMINATED	A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03619252	PHASE4	COMPLETED	Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
NCT03768960	PHASE4	COMPLETED	A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent
NCT03908138	PHASE4	UNKNOWN	RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
NCT04217967	PHASE4	COMPLETED	Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BORTEZOMIB	4	103
CARFILZOMIB	4	72
POMALIDOMIDE	4	67
DARATUMUMAB	4	62
LENALIDOMIDE	4	59
THALIDOMIDE	4	39
PLERIXAFOR	4	36
ZOLEDRONIC ACID ANHYDROUS	4	32
MELPHALAN	4	30
TACROLIMUS ANHYDROUS	4	30
ELOTUZUMAB	4	27
IXAZOMIB CITRATE	4	18
DOXORUBICIN	4	17
PANOBINOSTAT	4	16
ISATUXIMAB	4	13
CYCLOPHOSPHAMIDE ANHYDROUS	4	12
BENDAMUSTINE	4	11
SELINEXOR	4	11
BELANTAMAB MAFODOTIN	4	9
TECLISTAMAB	4	8
ROMIDEPSIN	4	6
ARSENIC TRIOXIDE	4	5
ELRANATAMAB	4	5
PALIFERMIN	4	5
TRIMETHOPRIM	4	5
VORINOSTAT	4	5
CARMUSTINE	4	4
CLOFARABINE	4	4
DIPHENHYDRAMINE	4	4
FLUDARABINE PHOSPHATE	4	4

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 21 predictive associations from 39 curated evidence items; also 6 prognostic, 4 oncogenic.

Molecular subtype	Therapy	Effect	Level	CIViC
CTAG1B Overexpression	Letetresgene Autoleucel	Sensitivity/Response	CIViC B	EID2940
CTAG2 Overexpression	Letetresgene Autoleucel	Sensitivity/Response	CIViC B	EID2941
KRAS G12A	Melphalan	Resistance	CIViC B	EID2009 +5
KRAS G12C	Melphalan	Resistance	CIViC B	EID2259 +4
KRAS G12D	Melphalan	Resistance	CIViC B	EID2248 +4
KRAS G12S	Melphalan	Resistance	CIViC B	EID2275 +4
BRAF V600E	Vemurafenib	Sensitivity/Response	CIViC C	EID1698 +1
CCND1 Overexpression	Bortezomib	Sensitivity/Response	CIViC C	EID7788
FGFR3 G802_X807del AND IGHA1::FGFR3 Fusion	Erdafitinib	Sensitivity/Response	CIViC C	EID11033
CRBN Mutation	Lenalidomide + Pomalidomide	Resistance	CIViC C	EID1766
FGFR3 F384L	Midostaurin	Sensitivity/Response	CIViC D	EID10410
FGFR3 K650E	R3Mab	Sensitivity/Response	CIViC D	EID10365
FGFR3 K650E	Midostaurin	Sensitivity/Response	CIViC D	EID10407
FGFR3 Overexpression	R3Mab	Sensitivity/Response	CIViC D	EID10364
FGFR3 Overexpression	Dovitinib	Sensitivity/Response	CIViC D	EID12294
FGFR3 Y373C	R3Mab	Sensitivity/Response	CIViC D	EID10366
FGFR3 Y373C	Midostaurin	Sensitivity/Response	CIViC D	EID10408
MCL1 Amplification	Mcl-1 Inhibitor MIK665	Sensitivity/Response	CIViC D	EID11768
MYC Overexpression	JQ-1	Sensitivity/Response	CIViC D	EID5505
MYCL EXPRESSION	I-BET151 + JQ1	Sensitivity/Response	CIViC D	EID1706
FGFR3 N540D	Midostaurin	Resistance	CIViC D	EID10411