CYRIB

Summary

CYRIB (CYFIP related Rac1 interactor B, HGNC:25216) is a protein-coding gene on chromosome 8q24.21, encoding CYFIP-related Rac1 interactor B (Q9NUQ9). Negatively regulates RAC1 signaling and RAC1-driven cytoskeletal remodeling.

Enables small GTPase binding activity. Involved in several processes, including cellular response to molecule of bacterial origin; negative regulation of small GTPase mediated signal transduction; and regulation of organelle organization. Located in mitochondrion.

Source: NCBI Gene 51571 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 32 total
• Druggable target: yes
• MANE Select transcript: NM_001353258

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25216
Approved symbol	CYRIB
Name	CYFIP related Rac1 interactor B
Location	8q24.21
Locus type	gene with protein product
Status	Approved
Aliases	BM-009, CYRI-B, CYRI
Ensembl gene	ENSG00000153310
Ensembl biotype	protein_coding
OMIM	617978
Entrez	51571

Gene structure

Transcript identifiers

Ensembl transcripts: 115 — 106 protein_coding, 5 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000401979, ENST00000517654, ENST00000517672, ENST00000517801, ENST00000518167, ENST00000518283, ENST00000518285, ENST00000518344, ENST00000518879, ENST00000519020, ENST00000519070, ENST00000519110, ENST00000519142, ENST00000519540, ENST00000519824, ENST00000520204, ENST00000520254, ENST00000520887, ENST00000521223, ENST00000522250, ENST00000522361, ENST00000522702, ENST00000522746, ENST00000522941, ENST00000523288, ENST00000523509, ENST00000523514, ENST00000523993, ENST00000694912, ENST00000699094, ENST00000703342, ENST00000897376, ENST00000897377, ENST00000897378, ENST00000897379, ENST00000897380, ENST00000897381, ENST00000897382, ENST00000897383, ENST00000897384, ENST00000897385, ENST00000897386, ENST00000897387, ENST00000897388, ENST00000897389, ENST00000897390, ENST00000897391, ENST00000897392, ENST00000897393, ENST00000897394, ENST00000897395, ENST00000897396, ENST00000897397, ENST00000897398, ENST00000897399, ENST00000897400, ENST00000897401, ENST00000897402, ENST00000897403, ENST00000897404, ENST00000897405, ENST00000932358, ENST00000932359, ENST00000932360, ENST00000932361, ENST00000932362, ENST00000932363, ENST00000932364, ENST00000932365, ENST00000932366, ENST00000932367, ENST00000932368, ENST00000932369, ENST00000932370, ENST00000932371, ENST00000932372, ENST00000954079, ENST00000954080, ENST00000954081, ENST00000954082, ENST00000954083, ENST00000954084, ENST00000954085, ENST00000954086, ENST00000954087, ENST00000954088, ENST00000954089, ENST00000954090, ENST00000954091, ENST00000954092, ENST00000954093, ENST00000954094, ENST00000954095, ENST00000954096, ENST00000954097, ENST00000954098, ENST00000954099, ENST00000954100, ENST00000954101, ENST00000954102, ENST00000954103, ENST00000954104, ENST00000954105, ENST00000954106, ENST00000954107, ENST00000954108, ENST00000954109, ENST00000954110, ENST00000954111, ENST00000954112, ENST00000954113, ENST00000954114, ENST00000954115, ENST00000954116, ENST00000954117

RefSeq mRNA: 78 — MANE Select: NM_001353258 NM_001256763, NM_001330612, NM_001353242, NM_001353243, NM_001353244, NM_001353245, NM_001353246, NM_001353247, NM_001353248, NM_001353249, NM_001353250, NM_001353251, NM_001353252, NM_001353253, NM_001353254, NM_001353255, NM_001353256, NM_001353257, NM_001353258, NM_001353259, NM_001353260, NM_001353261, NM_001353262, NM_001353263, NM_001353264, NM_001353265, NM_001353266, NM_001353267, NM_001353268, NM_001353269, NM_001353270, NM_001353271, NM_001353272, NM_001353273, NM_001353274, NM_001353275, NM_001353276, NM_001353277, NM_001353278, NM_001353279, NM_001353280, NM_001353281, NM_001353282, NM_001353283, NM_001353284, NM_001353285, NM_001353286, NM_001353287, NM_001353288, NM_001353289, NM_001353290, NM_001353291, NM_001353292, NM_001353293, NM_001353294, NM_001353295, NM_001353296, NM_001353297, NM_001353298, NM_001353299, NM_001353300, NM_001353301, NM_001353302, NM_001353303, NM_001353304, NM_001353305, NM_001353306, NM_001353307, NM_001353308, NM_001353309, NM_001353310, NM_001353311, NM_001353312, NM_001353313, NM_001353314, NM_001353315, NM_001353316, NM_016623

CCDS: CCDS6361, CCDS83327, CCDS94340

Canonical transcript exons

ENST00000694912 — 14 exons

Exon	Start	End
ENSE00001269067	129849243	129849369
ENSE00001377506	129903312	129903350
ENSE00001521833	129904499	129904585
ENSE00001553075	129970943	129970995
ENSE00001785488	129850835	129850914
ENSE00003234528	129839593	129842205
ENSE00003470530	129852162	129852278
ENSE00003538533	129855611	129855747
ENSE00003580652	129846804	129846874
ENSE00003596463	129879389	129879471
ENSE00003756623	129854266	129854343
ENSE00003787152	129871375	129871496
ENSE00003788192	129862229	129862334
ENSE00003963236	130016370	130016560

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 83.6648 / max 2848.3541, expressed in 1823 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94990	34.5939	1811
94996	25.2347	1460
94994	13.9730	1646
94998	7.6245	1638
94997	0.8230	485
94995	0.6163	270
94993	0.5851	272
205333	0.2144	86

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.88	gold quality
mononuclear cell	CL:0000842	98.87	gold quality
leukocyte	CL:0000738	98.86	gold quality
granulocyte	CL:0000094	98.34	gold quality
blood	UBERON:0000178	98.29	gold quality
bone marrow cell	CL:0002092	97.58	gold quality
bone marrow	UBERON:0002371	97.52	gold quality
cortical plate	UBERON:0005343	97.12	gold quality
vermiform appendix	UBERON:0001154	96.97	gold quality
lymph node	UBERON:0000029	96.96	gold quality
spleen	UBERON:0002106	96.59	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.56	gold quality
prefrontal cortex	UBERON:0000451	96.45	gold quality
adrenal tissue	UBERON:0018303	96.25	gold quality
spinal cord	UBERON:0002240	96.12	gold quality
ganglionic eminence	UBERON:0004023	95.97	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.83	gold quality
corpus callosum	UBERON:0002336	95.80	gold quality
caecum	UBERON:0001153	95.54	gold quality
trabecular bone tissue	UBERON:0002483	95.47	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.47	gold quality
embryo	UBERON:0000922	95.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.05	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.92	gold quality
frontal cortex	UBERON:0001870	94.83	gold quality
primary visual cortex	UBERON:0002436	94.80	gold quality
neocortex	UBERON:0001950	94.78	gold quality
caudate nucleus	UBERON:0001873	94.62	gold quality
cingulate cortex	UBERON:0003027	94.57	gold quality
anterior cingulate cortex	UBERON:0009835	94.56	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	40.66
E-HCAD-35	yes	37.11
E-HCAD-6	yes	34.28
E-HCAD-10	yes	33.90
E-MTAB-10287	yes	31.96
E-HCAD-13	yes	23.68
E-HCAD-1	yes	17.54
E-MTAB-6701	yes	17.25
E-MTAB-8410	yes	13.62
E-MTAB-10042	yes	8.04
E-CURD-88	yes	7.64
E-CURD-119	yes	5.21
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

156 targeting CYRIB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-96-5P	99.95	72.80	2140
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-22-3P	99.93	68.13	917

Literature-anchored findings (GeneRIF, showing 11)

• FAM49B is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• Three proteins-matrix metalloproteinase-9, neutrophil elastase, and FAM49B-were significantly lower in abundance in samples from women with endometriosis. (PMID:25284053)
• Low fam49B expression is associated with pancreatic ductal adenocarcinoma metastasis. (PMID:29059164)
• FAM49B inhibits T cell activation by repressing Rac activity and modulating cytoskeleton reorganization. (PMID:29632189)
• CYFIP related Rac1 interactor B (CYRI) binds to the small GTPase RAC1 through a conserved domain present in CYFIP proteins. CYRI negatively regulates RAC1 signalling, thereby attenuating processes such as macropinocytosis, phagocytosis and cell migration. This enables CYRI to counteract Salmonella at various stages of infection. The bacterial effector SopE, a RAC1 activator, selectively targets CYRI following infection. (PMID:31285585)
• TASP1 Promotes Gallbladder Cancer Cell Proliferation and Metastasis by Up-regulating FAM49B via PI3K/AKT Pathway. (PMID:32071545)
• Structural Basis of CYRI-B Direct Competition with Scar/WAVE Complex for Rac1. (PMID:33217330)
• GOLM1 and FAM49B: Potential Biomarkers in HNSCC Based on Bioinformatics and Immunohistochemical Analysis. (PMID:36499755)
• A genome-wide genetic screen identifies CYRI-B as a negative regulator of CEACAM3-mediated phagocytosis. (PMID:37264948)
• LANCL1, a cell surface protein, promotes liver tumor initiation through FAM49B-Rac1 axis to suppress oxidative stress. (PMID:37540188)
• CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake. (PMID:38712822)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam49ba	ENSDARG00000020929
danio_rerio	fam49bb	ENSDARG00000045417
mus_musculus	Cyrib	ENSMUSG00000022378
rattus_norvegicus	Cyrib	ENSRNOG00000061246
drosophila_melanogaster	CG32066	FBGN0052066
caenorhabditis_elegans		WBGENE00019944

Paralogs (1): CYRIA (ENSG00000197872)

Protein

Protein identifiers

CYFIP-related Rac1 interactor B — Q9NUQ9 (reviewed: Q9NUQ9)

Alternative names: L1

All UniProt accessions (12): Q9NUQ9, A0A8V8TMP7, E5RFS4, E5RGI7, E5RH75, E5RHU5, E5RI16, E5RIR8, E5RJE1, E5RJL8, E5RK61, E5RK81

UniProt curated annotations — full annotation on UniProt →

Function. Negatively regulates RAC1 signaling and RAC1-driven cytoskeletal remodeling. Regulates chemotaxis, cell migration and epithelial polarization by controlling the polarity, plasticity, duration and extent of protrusions. Limits Rac1 mediated activation of the Scar/WAVE complex, focuses protrusion signals and regulates pseudopod complexity by inhibiting Scar/WAVE-induced actin polymerization. Protects against Salmonella bacterial infection. Attenuates processes such as macropinocytosis, phagocytosis and cell migration and restrict sopE-mediated bacterial entry. Also restricts infection mediated by Mycobacterium tuberculosis and Listeria monocytogenes. Involved in the regulation of mitochondrial dynamics and oxidative stress.

Subunit / interactions. Interacts with RAC1 (GTP-bound form preferentially).

Subcellular location. Membrane. Mitochondrion.

Post-translational modifications. Ubiquitinated at Lys-74 upon Salmonella bacterial infection.

Induction. Protein levels are negatively regulated by Salmonella.

Similarity. Belongs to the CYRI family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NUQ9-1	1	yes
Q9NUQ9-2	2

RefSeq proteins (78): NP_001243692, NP_001317541, NP_001340171, NP_001340172, NP_001340173, NP_001340174, NP_001340175, NP_001340176, NP_001340177, NP_001340178, NP_001340179, NP_001340180, NP_001340181, NP_001340182, NP_001340183, NP_001340184, NP_001340185, NP_001340186, NP_001340187, NP_001340188, NP_001340189, NP_001340190, NP_001340191, NP_001340192, NP_001340193, NP_001340194, NP_001340195, NP_001340196, NP_001340197, NP_001340198, NP_001340199, NP_001340200, NP_001340201, NP_001340202, NP_001340203, NP_001340204, NP_001340205, NP_001340206, NP_001340207, NP_001340208, NP_001340209, NP_001340210, NP_001340211, NP_001340212, NP_001340213, NP_001340214, NP_001340215, NP_001340216, NP_001340217, NP_001340218, NP_001340219, NP_001340220, NP_001340221, NP_001340222, NP_001340223, NP_001340224, NP_001340225, NP_001340226, NP_001340227, NP_001340228, NP_001340229, NP_001340230, NP_001340231, NP_001340232, NP_001340233, NP_001340234, NP_001340235, NP_001340236, NP_001340237, NP_001340238, NP_001340239, NP_001340240, NP_001340241, NP_001340242, NP_001340243, NP_001340244, NP_001340245, NP_057707 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009828	CYRIA/CYRIB_Rac1-bd	Domain
IPR039789	CYRI	Family

Pfam: PF07159

UniProt features (9 total): mutagenesis site 3, initiator methionine 1, chain 1, lipid moiety-binding region 1, cross-link 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7AJK	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NUQ9-F1	92.09	0.87

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 2, 74

Mutagenesis-validated functional residues (3):

Position	Phenotype
150	no effect on interaction with rac1. almost abolishes interaction with rac1; when associated with d-161.
160–161	abolishes interaction with rac1.
161	strongly decreases interaction with rac1. almost abolishes interaction with rac1; when associated with d-150.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation

MSigDB gene sets: 316 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, MCLACHLAN_DENTAL_CARIES_UP, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION

GO Biological Process (12): positive regulation of T cell mediated cytotoxicity (GO:0001916), regulation of cell migration (GO:0030334), negative regulation of actin filament polymerization (GO:0030837), positive regulation of type II interferon production (GO:0032729), positive regulation of T cell activation (GO:0050870), regulation of chemotaxis (GO:0050920), negative regulation of small GTPase mediated signal transduction (GO:0051058), cellular response to molecule of bacterial origin (GO:0071219), regulation of mitochondrial fission (GO:0090140), regulation of establishment of cell polarity (GO:2000114), positive regulation of memory T cell activation (GO:2000568), regulation of actin filament polymerization (GO:0030833)

GO Molecular Function (3): MHC class Ib protein binding, via antigen binding groove (GO:0023030), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), mitochondrion (GO:0005739), cilium (GO:0005929), membrane (GO:0016020), platelet alpha granule lumen (GO:0031093), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
actin filament polymerization	2
cellular anatomical structure	2
positive regulation of leukocyte mediated cytotoxicity	1
T cell mediated cytotoxicity	1
regulation of T cell mediated cytotoxicity	1
positive regulation of T cell mediated immunity	1
cell migration	1
regulation of cell motility	1
regulation of actin filament polymerization	1
negative regulation of protein polymerization	1
negative regulation of cytoskeleton organization	1
negative regulation of supramolecular fiber organization	1
positive regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
T cell activation	1
regulation of T cell activation	1
positive regulation of lymphocyte activation	1
positive regulation of leukocyte cell-cell adhesion	1
chemotaxis	1
regulation of response to external stimulus	1
regulation of locomotion	1
small GTPase-mediated signal transduction	1
regulation of small GTPase mediated signal transduction	1
negative regulation of intracellular signal transduction	1
response to molecule of bacterial origin	1
cellular response to biotic stimulus	1
mitochondrial fission	1
regulation of mitochondrion organization	1
regulation of anatomical structure morphogenesis	1
establishment of cell polarity	1
regulation of establishment or maintenance of cell polarity	1
memory T cell activation	1
positive regulation of T cell activation	1
regulation of memory T cell activation	1
regulation of actin polymerization or depolymerization	1
regulation of protein polymerization	1
MHC class Ib protein complex binding	1
MHC class Ib protein binding	1
GTPase binding	1

Protein interactions and networks

STRING

666 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYRIB	SNCA	P37840	537
CYRIB	TASP1	Q9H6P5	459
CYRIB	MCCC1	Q96RQ3	454
CYRIB	TMEM175	Q9BSA9	453
CYRIB	EPB41L1	Q9H4G0	451
CYRIB	THSD4	Q6ZMP0	449
CYRIB	ACTN1	P12814	436
CYRIB	ACTN2	P35609	427
CYRIB	UGT8	Q16880	425
CYRIB	EGFR	P00533	421
CYRIB	GATD3	P0DPI2	421
CYRIB	GSK3B	P49841	412
CYRIB	KPNA1	P52294	411
CYRIB	CYFIP2	Q96F07	403
CYRIB	CDK2	P24941	400

IntAct

93 interactions, top by confidence:

A	B	Type	Score
STAM	HGS	psi-mi:“MI:0914”(association)	0.860
PRELID1	TRIAP1	psi-mi:“MI:0914”(association)	0.730
CYRIA	CYRIB	psi-mi:“MI:0915”(physical association)	0.670
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
NIF3L1	CYRIB	psi-mi:“MI:0915”(physical association)	0.560
CYRIB	NIF3L1	psi-mi:“MI:0915”(physical association)	0.560
HIP1	CYRIB	psi-mi:“MI:0915”(physical association)	0.560
CYRIB	BAG6	psi-mi:“MI:0915”(physical association)	0.560
KLF11	CYRIB	psi-mi:“MI:0915”(physical association)	0.560
CYRIB	RAB3IL1	psi-mi:“MI:0914”(association)	0.530
WASHC3	WASH3P	psi-mi:“MI:0914”(association)	0.530
TIMMDC1	NDUFS8	psi-mi:“MI:0914”(association)	0.530
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
GPS1	PXDNL	psi-mi:“MI:0914”(association)	0.530
MSRB2	BLTP3B	psi-mi:“MI:0914”(association)	0.530
POU2F2	CYRIB	psi-mi:“MI:0915”(physical association)	0.400
CYRIB		psi-mi:“MI:0915”(physical association)	0.370
CYRIB	MAPK6	psi-mi:“MI:0915”(physical association)	0.370
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
P2RY6	RAVER1	psi-mi:“MI:0914”(association)	0.350
GTF2E2	UBA6	psi-mi:“MI:0914”(association)	0.350
NUFIP1	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
DNAAF2	DNM1L	psi-mi:“MI:0914”(association)	0.350

BioGRID (111): NIF3L1 (Two-hybrid), FAM49B (Affinity Capture-MS), FAM49B (Affinity Capture-MS), FAM49A (Affinity Capture-MS), CDK19 (Affinity Capture-MS), FAM49B (Affinity Capture-RNA), FAM49B (Co-fractionation), FAM49B (Co-fractionation), FAM49B (Co-fractionation), FAM49B (Co-fractionation), PCBP1 (Co-fractionation), PPIL3 (Co-fractionation), TALDO1 (Co-fractionation), FAM49A (Affinity Capture-MS), FAM49B (Affinity Capture-MS)

ESM2 similar proteins: A4FUI1, B3DL65, B5FX56, B5X5N3, B5X9S3, F1QN74, F4IK01, O94740, P22468, P47149, P70281, P97357, Q09858, Q0WQE7, Q14D04, Q16VW9, Q2KJI3, Q3SYZ9, Q4R6I5, Q4R7B1, Q4VC31, Q561Q8, Q561X3, Q5M8Y7, Q5XG48, Q5XIR8, Q5XK92, Q5ZLS8, Q5ZMJ7, Q60547, Q61QK6, Q63520, Q68CZ6, Q6DCY9, Q6GPT7, Q6IR70, Q6PBK1, Q6TNU3, Q8C6S9, Q8K2A7

Diamond homologs: Q17QT7, Q2KJI3, Q5R6L2, Q5ZI04, Q8BHZ0, Q8T2H0, Q921M7, Q9H0Q0, Q9NUQ9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

32 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3047 predictions. Top by Δscore:

Variant	Effect	Δscore
8:129842205:CCTAA:C	acceptor_loss	1.0000
8:129842206:CTAAA:C	acceptor_loss	1.0000
8:129842207:T:A	acceptor_loss	1.0000
8:129846874:TC:T	acceptor_loss	1.0000
8:129846875:C:CA	acceptor_loss	1.0000
8:129846875:C:CC	acceptor_gain	1.0000
8:129849241:A:AC	donor_gain	1.0000
8:129849242:C:CC	donor_gain	1.0000
8:129850915:C:CC	acceptor_gain	1.0000
8:129850927:A:C	acceptor_gain	1.0000
8:129852157:CTTAC:C	donor_loss	1.0000
8:129852159:TACC:T	donor_loss	1.0000
8:129852160:A:AC	donor_gain	1.0000
8:129852161:C:CC	donor_gain	1.0000
8:129852161:CCT:C	donor_gain	1.0000
8:129852275:CTGC:C	acceptor_gain	1.0000
8:129852276:TGC:T	acceptor_gain	1.0000
8:129852277:GC:G	acceptor_gain	1.0000
8:129852278:CCTG:C	acceptor_gain	1.0000
8:129852279:C:CC	acceptor_gain	1.0000
8:129852281:G:C	acceptor_gain	1.0000
8:129852281:G:GC	acceptor_gain	1.0000
8:129854260:ACTT:A	donor_loss	1.0000
8:129854261:CTT:C	donor_loss	1.0000
8:129854263:T:TG	donor_loss	1.0000
8:129854264:A:AC	donor_gain	1.0000
8:129854265:C:CC	donor_gain	1.0000
8:129854340:TCAT:T	acceptor_gain	1.0000
8:129854341:CAT:C	acceptor_gain	1.0000
8:129854341:CATC:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000032796 (8:129948983 T>C,G), RS1000034779 (8:129839257 G>A,C), RS1000060876 (8:129858649 G>T), RS1000064596 (8:129991865 C>A,T), RS1000071518 (8:129863718 A>T), RS1000079044 (8:129970606 T>C,G), RS1000081516 (8:129865519 T>C), RS1000101167 (8:129947635 G>A,T), RS1000106872 (8:129970419 C>T), RS1000118674 (8:129858367 C>A), RS1000128696 (8:129985222 T>C), RS1000141827 (8:129928666 AAAAAAAG>A), RS1000159670 (8:129973929 T>A), RS1000169317 (8:129916110 G>A), RS1000175237 (8:130014399 C>G)

Disease associations

OMIM: gene MIM:617978 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST000189_42	Protein quantitative trait loci	6.000000e-06
GCST001137_6	White blood cell count	3.000000e-20
GCST002037_11	Post-traumatic stress disorder (asjusted for relatedness)	7.000000e-07
GCST004627_48	Lymphocyte count	1.000000e-10
GCST007843_13	Rheumatoid arthritis	2.000000e-10
GCST008023_1	Sour taste perception in obesity with metabolic syndrome	2.000000e-06
GCST009325_48	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	2.000000e-08
GCST009391_17	Metabolite levels	2.000000e-06
GCST009391_1921	Metabolite levels	4.000000e-06
GCST009391_592	Metabolite levels	8.000000e-06
GCST90002385_372	High light scatter reticulocyte count	4.000000e-13
GCST90002386_417	High light scatter reticulocyte percentage of red cells	2.000000e-12
GCST90002388_212	Lymphocyte count	2.000000e-20
GCST90002389_341	Lymphocyte percentage of white cells	8.000000e-14
GCST90002391_236	Mean corpuscular hemoglobin concentration	4.000000e-14
GCST90002396_441	Mean reticulocyte volume	7.000000e-10
GCST90002397_667	Mean spheric corpuscular volume	1.000000e-58
GCST90002402_83	Platelet count	6.000000e-19
GCST90002404_102	Red cell distribution width	1.000000e-15
GCST90002405_525	Reticulocyte count	5.000000e-16
GCST90002406_315	Reticulocyte fraction of red cells	8.000000e-15

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004809	fructose-bisphosphate aldolase measurement
EFO:0005091	monocyte count
EFO:0004587	lymphocyte count
EFO:0010464	beta-aminoisobutyric acid measurement
EFO:0010501	indole-3-propionate measurement
EFO:0007986	reticulocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0010701	mean reticulocyte volume
EFO:0004309	platelet count
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067202 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.31	Kd	4849	nM	CHEMBL3752910
5.31	ED50	4849	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148364: Binding affinity to human FAM49B incubated for 45 mins by Kinobead based pull down assay	kd	4.8486	uM

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases abundance	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Nickel	increases expression	2
Smoke	decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	2
Valproic Acid	decreases methylation, increases expression	2
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Arbutin	increases expression	1
Cadmium	increases abundance, increases palmitoylation, decreases reaction	1
Coumestrol	decreases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651406	Binding	Binding affinity to human FAM49B incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1PQ	Abcam HeLa CYRIB KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.