FAM222B

Summary

FAM222B (family with sequence similarity 222 member B, HGNC:25563) is a protein-coding gene on chromosome 17q11.2, encoding Protein FAM222B (Q8WU58).

Located in nucleoplasm.

Source: NCBI Gene 55731 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 85 total
• Druggable target: yes
• MANE Select transcript: NM_001077498

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25563
Approved symbol	FAM222B
Name	family with sequence similarity 222 member B
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10700
Ensembl gene	ENSG00000173065
Ensembl biotype	protein_coding
Entrez	55731

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 33 protein_coding, 1 nonsense_mediated_decay

ENST00000341217, ENST00000452648, ENST00000577376, ENST00000577513, ENST00000577682, ENST00000579381, ENST00000581229, ENST00000581407, ENST00000582059, ENST00000582266, ENST00000583307, ENST00000583522, ENST00000583953, ENST00000584059, ENST00000874874, ENST00000874875, ENST00000874876, ENST00000874877, ENST00000874878, ENST00000874879, ENST00000874880, ENST00000919307, ENST00000919308, ENST00000919309, ENST00000919310, ENST00000919311, ENST00000919312, ENST00000919313, ENST00000919314, ENST00000919315, ENST00000919316, ENST00000919317, ENST00000919318, ENST00000919319

RefSeq mRNA: 12 — MANE Select: NM_001077498 NM_001077498, NM_001288631, NM_001288632, NM_001288633, NM_001288634, NM_001288635, NM_001288636, NM_001288637, NM_001288638, NM_001288639, NM_001288640, NM_018182

CCDS: CCDS45637

Canonical transcript exons

ENST00000581407 — 3 exons

Exon	Start	End
ENSE00002698491	28842682	28842790
ENSE00002713974	28755980	28759876
ENSE00003919538	28766586	28766707

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 97.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.8610 / max 175.0210, expressed in 1807 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165079	13.0410	1792
165077	4.7679	1562
165076	0.3450	159
165078	0.2327	89
165080	0.2034	80
165073	0.1325	60
208113	0.1217	41
165081	0.0168	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.50	gold quality
oocyte	CL:0000023	96.20	gold quality
secondary oocyte	CL:0000655	95.96	gold quality
male germ cell	CL:0000015	95.76	gold quality
cervix squamous epithelium	UBERON:0006922	95.61	silver quality
tibialis anterior	UBERON:0001385	91.28	silver quality
nipple	UBERON:0002030	91.02	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.85	gold quality
renal medulla	UBERON:0000362	90.75	gold quality
gastrocnemius	UBERON:0001388	90.56	gold quality
cerebellar vermis	UBERON:0004720	90.55	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.12	gold quality
inferior vagus X ganglion	UBERON:0005363	90.04	gold quality
pylorus	UBERON:0001166	89.94	gold quality
choroid plexus epithelium	UBERON:0003911	89.77	gold quality
cardia of stomach	UBERON:0001162	89.57	gold quality
ventral tegmental area	UBERON:0002691	89.28	gold quality
visceral pleura	UBERON:0002401	89.26	gold quality
muscle of leg	UBERON:0001383	89.17	gold quality
ileal mucosa	UBERON:0000331	88.64	silver quality
epithelium of mammary gland	UBERON:0003244	88.35	gold quality
CA1 field of hippocampus	UBERON:0003881	88.33	gold quality
trachea	UBERON:0003126	88.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.16	gold quality
body of tongue	UBERON:0011876	88.14	gold quality
mammary duct	UBERON:0001765	88.03	gold quality
testis	UBERON:0000473	87.99	gold quality
dorsal plus ventral thalamus	UBERON:0001897	87.98	gold quality
subthalamic nucleus	UBERON:0001906	87.91	gold quality
left testis	UBERON:0004533	87.87	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.76
E-CURD-10	no	237.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

189 targeting FAM222B, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam222ba	ENSDARG00000059886
danio_rerio	fam222bb	ENSDARG00000078578
mus_musculus	Fam222b	ENSMUSG00000037750
rattus_norvegicus	Fam222b	ENSRNOG00000029570

Paralogs (1): FAM222A (ENSG00000139438)

Protein

Protein identifiers

Protein FAM222B — Q8WU58 (reviewed: Q8WU58)

All UniProt accessions (7): Q8WU58, J3KSK8, J3QKY8, J3QLP2, J3QR32, J3QRM5, J3QRR9

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the FAM222 family.

RefSeq proteins (12): NP_001070966, NP_001275560, NP_001275561, NP_001275562, NP_001275563, NP_001275564, NP_001275565, NP_001275566, NP_001275567, NP_001275568, NP_001275569, NP_060652 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029340	FAM222	Family

Pfam: PF15258

UniProt features (11 total): region of interest 3, sequence conflict 3, compositionally biased region 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WU58-F1	48.21	0.02

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 132 (showing top): AAGCAAT_MIR137, PAX4_01, TGCGCANK_UNKNOWN, HATADA_METHYLATED_IN_LUNG_CANCER_DN, chr17q11, YY1_02, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, ACEVEDO_LIVER_CANCER_UP, TGCCTTA_MIR124A, GSE13762_CTRL_VS_125_VITAMIND_DAY12_DC_DN, ACACTGG_MIR199A_MIR199B, MIKKELSEN_ES_ICP_WITH_H3K4ME3, MIKKELSEN_NPC_ICP_WITH_H3K4ME3, MTF1_Q4, DCA_UP.V1_DN

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): nucleoplasm (GO:0005654), mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

228 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM222B	PDZD9	Q8IXQ8	642
FAM222B	OR51D1	Q8NGF3	526
FAM222B	ZNF572	Q7Z3I7	489
FAM222B	SSC4D	Q8WTU2	484
FAM222B	CEP152	O94986	474
FAM222B	OR2K2	Q8NGT1	463
FAM222B	ZNF789	Q5FWF6	453
FAM222B	TRMT10B	Q6PF06	447
FAM222B	ZNF695	Q8IW36	431
FAM222B	FAM177A1	Q8N128	430
FAM222B	THUMPD2	Q9BTF0	430
FAM222B	LMBR1L	Q6UX01	390
FAM222B	SLC1A6	P48664	378
FAM222B	BEAN1	Q3B7T3	370
FAM222B	NUFIP2	Q7Z417	360

IntAct

116 interactions, top by confidence:

A	B	Type	Score
FAM222B	CYSRT1	psi-mi:“MI:0915”(physical association)	0.560
FAM222B	SPAG8	psi-mi:“MI:0915”(physical association)	0.560
FAM222B	SMUG1	psi-mi:“MI:0915”(physical association)	0.560
FAM222B	EIF3F	psi-mi:“MI:0915”(physical association)	0.560
FAM222B	AKAP8L	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	FAM222B	psi-mi:“MI:0915”(physical association)	0.560
FAM222B	ANKRD10	psi-mi:“MI:0915”(physical association)	0.560
SMUG1	FAM222B	psi-mi:“MI:0915”(physical association)	0.560
EIF3F	FAM222B	psi-mi:“MI:0915”(physical association)	0.560
PRR20D	FAM222B	psi-mi:“MI:0915”(physical association)	0.560
BANP	FAM222B	psi-mi:“MI:0915”(physical association)	0.560
FHL3	FAM222B	psi-mi:“MI:0915”(physical association)	0.560
TRIP6	FAM222B	psi-mi:“MI:0915”(physical association)	0.560
FAM222B	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP11-1	FAM222B	psi-mi:“MI:0915”(physical association)	0.560
TTLL12	FAM222B	psi-mi:“MI:0915”(physical association)	0.560
FAM222B	KRTAP3-1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP26-1	FAM222B	psi-mi:“MI:0915”(physical association)	0.560
FAM222B	LRRC61	psi-mi:“MI:0915”(physical association)	0.560
ACTMAP	FAM222B	psi-mi:“MI:0915”(physical association)	0.560
SOHLH1	FAM222B	psi-mi:“MI:0915”(physical association)	0.560
FAM222B	CNFN	psi-mi:“MI:0915”(physical association)	0.560
UFSP1	FAM222B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (45): FAM222B (Two-hybrid), FAM222B (Two-hybrid), FAM222B (Two-hybrid), FAM222B (Two-hybrid), FAM222B (Two-hybrid), FAM222B (Two-hybrid), FAM222B (Two-hybrid), FAM222B (Two-hybrid), FAM222B (Two-hybrid), FAM222B (Two-hybrid), FAM222B (Two-hybrid), FAM222B (Two-hybrid), FAM222B (Two-hybrid), FAM222B (Two-hybrid), FAM222B (Two-hybrid)

ESM2 similar proteins: A0A096MJY4, A0A1L8H0H2, A1L2P5, A2ICN5, A2VDZ3, A4UTP7, B1AYB6, F8VPJ6, O54826, O94900, P19538, P22199, P23682, P55197, P91607, P91686, P91705, P91943, Q02078, Q03413, Q03414, Q06413, Q1KKS7, Q2KHR2, Q2KIA0, Q2MJT0, Q3LHL9, Q3V5Z9, Q5R444, Q5REW7, Q60929, Q66JW3, Q6P539, Q6YXY2, Q8BUR3, Q8CFN5, Q8VII8, Q8WU58, Q8WYQ9, Q91690

Diamond homologs: Q5U5X8, Q6PGH4, Q8WU58, Q6P539

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1687 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28842680:A:AC	donor_gain	1.0000
17:28842681:C:CC	donor_gain	1.0000
17:28842681:CGGT:C	donor_gain	1.0000
17:28759765:C:CC	acceptor_gain	0.9900
17:28766584:A:AC	donor_gain	0.9900
17:28766585:C:CC	donor_gain	0.9900
17:28766585:CATTT:C	donor_gain	0.9900
17:28766704:CACA:C	acceptor_gain	0.9900
17:28766706:CA:C	acceptor_gain	0.9900
17:28766708:C:CC	acceptor_gain	0.9900
17:28779108:TAG:T	donor_gain	0.9900
17:28790709:T:A	donor_gain	0.9900
17:28806435:T:TA	donor_gain	0.9900
17:28806470:T:TA	donor_gain	0.9900
17:28842676:ACT:A	donor_loss	0.9900
17:28842677:C:CG	donor_loss	0.9900
17:28842678:T:TG	donor_loss	0.9900
17:28842679:C:CG	donor_loss	0.9900
17:28842680:A:AG	donor_loss	0.9900
17:28842680:ACGGT:A	donor_gain	0.9900
17:28842681:C:CT	donor_loss	0.9900
17:28842681:CG:C	donor_gain	0.9900
17:28842681:CGG:C	donor_gain	0.9900
17:28842681:CGGTC:C	donor_gain	0.9900
17:28759763:CA:C	acceptor_gain	0.9800
17:28766703:TCACA:T	acceptor_gain	0.9800
17:28766704:CACAC:C	acceptor_gain	0.9800
17:28779109:A:AC	donor_gain	0.9800
17:28806431:T:TA	donor_gain	0.9800
17:28823106:A:AC	acceptor_gain	0.9800

AlphaMissense

3651 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:28759773:G:C	F62L	1.000
17:28759773:G:T	F62L	1.000
17:28759774:A:G	F62S	1.000
17:28759775:A:G	F62L	1.000
17:28759777:A:G	I61T	1.000
17:28759783:A:C	I59R	1.000
17:28759783:A:T	I59K	1.000
17:28759813:G:T	A49D	1.000
17:28759825:A:G	L45S	1.000
17:28759071:G:C	S296R	0.999
17:28759071:G:T	S296R	0.999
17:28759073:T:G	S296R	0.999
17:28759091:C:G	G290R	0.999
17:28759095:A:C	C288W	0.999
17:28759096:C:T	C288Y	0.999
17:28759097:A:G	C288R	0.999
17:28759131:G:C	C276W	0.999
17:28759132:C:T	C276Y	0.999
17:28759133:A:G	C276R	0.999
17:28759144:A:G	I272T	0.999
17:28759213:A:C	I249S	0.999
17:28759213:A:G	I249T	0.999
17:28759213:A:T	I249N	0.999
17:28759756:A:T	V68D	0.999
17:28759774:A:C	F62C	0.999
17:28759777:A:C	I61S	0.999
17:28759777:A:T	I61N	0.999
17:28759783:A:G	I59T	0.999
17:28759789:A:G	L57P	0.999
17:28759814:C:G	A49P	0.999

dbSNP variants (sampled 300 via entrez): RS1000007106 (17:28826133 G>A,C), RS1000024785 (17:28818810 G>A), RS1000095529 (17:28851242 C>A,T), RS1000105876 (17:28803945 C>T), RS1000115745 (17:28817932 T>C), RS1000159003 (17:28800217 C>T), RS1000180763 (17:28842827 G>A), RS1000211162 (17:28828197 G>A,C), RS1000231537 (17:28755526 T>G), RS1000246973 (17:28827828 G>C), RS1000276232 (17:28768167 A>G), RS1000340552 (17:28849177 C>A,T), RS1000354787 (17:28819339 C>T), RS1000364363 (17:28759881 A>G), RS1000386591 (17:28761750 A>G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:619575

GenCC curated gene-disease

Mondo (1): developmental delay with or without intellectual impairment or behavioral abnormalities (MONDO:0859199)

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST004602_290	Mean corpuscular volume	3.000000e-35
GCST004605_21	Mean corpuscular hemoglobin concentration	3.000000e-44
GCST004621_188	Red cell distribution width	2.000000e-70
GCST004630_212	Mean corpuscular hemoglobin	9.000000e-65
GCST006011_47	Mean corpuscular volume	4.000000e-09
GCST008837_5	Estimated glomerular filtration rate reduction (30%)	9.000000e-06
GCST90002384_408	Hemoglobin	1.000000e-16
GCST90002390_108	Mean corpuscular hemoglobin	4.000000e-161
GCST90002391_90	Mean corpuscular hemoglobin concentration	5.000000e-81
GCST90002392_12	Mean corpuscular volume	3.000000e-103
GCST90002403_355	Red blood cell count	4.000000e-24

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066370 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.96	Kd	110.4	nM	CHEMBL5653589
6.74	ED50	180.8	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148363: Binding affinity to human FAM222B incubated for 45 mins by Kinobead based pull down assay	kd	0.1104	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
Zoledronic Acid	decreases expression	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Coumestrol	decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects cotreatment, increases expression	1
Manganese	decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Dronabinol	increases expression	1
Theophylline	affects cotreatment, increases expression	1
Tunicamycin	decreases expression	1
Urethane	increases expression	1
Vitamin E	decreases expression	1
Cyclosporine	increases expression	1
Copper Sulfate	increases expression	1
Vitamin K 3	affects 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
CHEMBL5651405	Binding	Binding affinity to human FAM222B 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

Clinical trials (associated diseases)

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