FAM222A

Summary

FAM222A (family with sequence similarity 222 member A, HGNC:25915) is a protein-coding gene on chromosome 12q24.11, encoding Protein FAM222A (Q5U5X8).

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 105 total — 1 likely-pathogenic
• MANE Select transcript: NM_032829

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25915
Approved symbol	FAM222A
Name	family with sequence similarity 222 member A
Location	12q24.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14721
Ensembl gene	ENSG00000139438
Ensembl biotype	protein_coding
Entrez	84915

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000358906, ENST00000538780, ENST00000543653, ENST00000898959, ENST00000948520

RefSeq mRNA: 1 — MANE Select: NM_032829 NM_032829

CCDS: CCDS9133

Canonical transcript exons

ENST00000538780 — 3 exons

Exon	Start	End
ENSE00001423093	109744101	109744228
ENSE00002215649	109713825	109714897
ENSE00002240651	109768012	109770495

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 92.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.8066 / max 1016.4098, expressed in 1049 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127953	8.6982	1038
127955	0.1083	46

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	92.26	gold quality
spinal cord	UBERON:0002240	91.23	gold quality
inferior vagus X ganglion	UBERON:0005363	87.35	gold quality
substantia nigra	UBERON:0002038	86.25	gold quality
left testis	UBERON:0004533	85.60	gold quality
midbrain	UBERON:0001891	85.52	gold quality
right testis	UBERON:0004534	84.98	gold quality
putamen	UBERON:0001874	84.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.76	gold quality
pituitary gland	UBERON:0000007	84.72	gold quality
adenohypophysis	UBERON:0002196	84.67	gold quality
adrenal tissue	UBERON:0018303	84.00	gold quality
medial globus pallidus	UBERON:0002477	83.90	gold quality
testis	UBERON:0000473	83.80	gold quality
islet of Langerhans	UBERON:0000006	83.50	gold quality
hypothalamus	UBERON:0001898	83.27	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.89	gold quality
right adrenal gland	UBERON:0001233	82.42	gold quality
left adrenal gland	UBERON:0001234	82.32	gold quality
globus pallidus	UBERON:0001875	82.32	gold quality
left adrenal gland cortex	UBERON:0035825	82.32	gold quality
caudate nucleus	UBERON:0001873	82.22	gold quality
right adrenal gland cortex	UBERON:0035827	82.13	gold quality
subthalamic nucleus	UBERON:0001906	82.04	gold quality
adrenal cortex	UBERON:0001235	81.84	gold quality
adrenal gland	UBERON:0002369	81.55	gold quality
Ammon’s horn	UBERON:0001954	81.38	gold quality
corpus callosum	UBERON:0002336	81.06	gold quality
postcentral gyrus	UBERON:0002581	80.76	gold quality
dorsal plus ventral thalamus	UBERON:0001897	80.48	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	10.57
E-ANND-3	no	2.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

76 targeting FAM222A, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4650-5P	99.98	64.69	999
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-6825-5P	99.96	69.81	3431
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767

Literature-anchored findings (GeneRIF, showing 2)

• Study reports FAM222A as a putative brain atrophy susceptibility gene. The protein encoded by FAM222A is predominantly expressed in the CNS and is increased in brains of patients with Alzheimer’s disease (AD) and in an AD mouse model. It accumulates within amyloid deposits, physically interacts with amyloid-beta (Abeta) via its N-terminal Abeta binding domain and facilitates Abeta aggregation. (PMID:31964863)
• FAM222A, Part of the BET-Regulated Basal Endothelial Transcriptome, Is a Novel Determinant of Endothelial Biology and Angiogenesis-Brief Report. (PMID:37942611)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam222ab	ENSDARG00000087585
danio_rerio	fam222aa	ENSDARG00000090797
mus_musculus	Fam222a	ENSMUSG00000041930
rattus_norvegicus	Fam222a	ENSRNOG00000001198

Paralogs (1): FAM222B (ENSG00000173065)

Protein

Protein identifiers

Protein FAM222A — Q5U5X8 (reviewed: Q5U5X8)

All UniProt accessions (1): Q5U5X8

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the FAM222 family.

RefSeq proteins (1): NP_116218* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029340	FAM222	Family

Pfam: PF15258

UniProt features (4 total): sequence conflict 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5U5X8-F1	49.98	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 71 (showing top): CAGCTG_AP4_Q5, BILD_E2F3_ONCOGENIC_SIGNATURE, GGTGAAG_MIR412, GEORGES_TARGETS_OF_MIR192_AND_MIR215, chr12q24, LU_EZH2_TARGETS_UP, E2F3_UP.V1_UP, GSE13547_WT_VS_ZFX_KO_BCELL_ANTI_IGM_STIM_12H_UP, E2F5_TARGET_GENES, FOXN3_TARGET_GENES, HSD17B8_TARGET_GENES, KMT2D_TARGET_GENES, SKIL_TARGET_GENES, TAFAZZIN_TARGET_GENES, ZNF592_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

302 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM222A	TBCCD1	Q9NVR7	478
FAM222A	ANKRD13D	Q6ZTN6	465
FAM222A	C7orf57	Q8NEG2	460
FAM222A	SAXO4	Q7Z5V6	456
FAM222A	FAM220A	Q7Z4H9	434
FAM222A	FRMPD1	Q5SYB0	434
FAM222A	B3GNT4	Q9C0J1	430
FAM222A	SCYL1	Q96KG9	424
FAM222A	MBIP	Q9NS73	418
FAM222A	DDHD2	O94830	391
FAM222A	SLC75A1	Q14728	390
FAM222A	NOM1	Q5C9Z4	389
FAM222A	BRME1	Q0VDD7	371
FAM222A	MRPL52	Q86TS9	367
FAM222A	FAM89A	Q96GI7	364

IntAct

6 interactions, top by confidence:

A	B	Type	Score
FAM222A	MEIS1	psi-mi:“MI:0914”(association)	0.530
CFTR	FAM222A	psi-mi:“MI:0915”(physical association)	0.370
NLK	BACH1	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): MEIS2 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), MAB21L1 (Affinity Capture-MS), PBX2 (Affinity Capture-MS), PBX3 (Affinity Capture-MS), PBX1 (Affinity Capture-MS), NLK (Affinity Capture-MS), FAM222A (Affinity Capture-MS), FAM222A (Affinity Capture-MS), FAM222A (Affinity Capture-MS), FAM222A (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), MEIS2 (Affinity Capture-MS), MAB21L1 (Affinity Capture-MS), NLK (Affinity Capture-MS)

ESM2 similar proteins: A2A9A2, A2D4R4, A2D649, A2T6H5, A2T7H5, D3YWE6, E9PYL2, O15054, O15353, O15417, O35126, O43365, P02831, P18111, P31260, P31310, P47902, P50548, P54259, P70459, P78411, P78413, P78414, P78415, P81066, P81067, P81068, Q08DG7, Q10571, Q2HJ78, Q2VWA4, Q3UHR0, Q5IS70, Q5NCY0, Q5TGY3, Q5U5X8, Q61572, Q64HY5, Q6PAL7, Q6PGH4

Diamond homologs: Q5U5X8, Q6PGH4, Q8WU58

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	87
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
402150	NM_032829.3(FAM222A):c.284A>T (p.His95Leu)	Likely pathogenic

SpliceAI

590 predictions. Top by Δscore:

Variant	Effect	Δscore
12:109744099:AG:A	acceptor_gain	1.0000
12:109744100:GG:G	acceptor_gain	1.0000
12:109768009:CAGG:C	acceptor_loss	1.0000
12:109768010:A:AG	acceptor_gain	1.0000
12:109768010:AG:A	acceptor_gain	1.0000
12:109768010:AGG:A	acceptor_loss	1.0000
12:109768010:AGGC:A	acceptor_gain	1.0000
12:109768010:AGGCG:A	acceptor_gain	1.0000
12:109768011:G:GG	acceptor_gain	1.0000
12:109768011:GG:G	acceptor_gain	1.0000
12:109768011:GGC:G	acceptor_gain	1.0000
12:109768011:GGCG:G	acceptor_gain	1.0000
12:109768011:GGCGA:G	acceptor_gain	1.0000
12:109714894:TCCGG:T	donor_loss	0.9900
12:109714896:CGGTG:C	donor_loss	0.9900
12:109714898:G:A	donor_loss	0.9900
12:109714898:G:GG	donor_gain	0.9900
12:109714899:T:G	donor_loss	0.9900
12:109744096:TGCA:T	acceptor_loss	0.9900
12:109744097:GCA:G	acceptor_loss	0.9900
12:109744098:CA:C	acceptor_loss	0.9900
12:109744099:A:AG	acceptor_gain	0.9900
12:109744100:G:GA	acceptor_loss	0.9900
12:109744100:G:GG	acceptor_gain	0.9900
12:109744227:GT:G	donor_gain	0.9900
12:109744229:G:GG	donor_gain	0.9900
12:109768008:ACAG:A	acceptor_gain	0.9900
12:109714894:TCCG:T	donor_gain	0.9800
12:109714896:CG:C	donor_gain	0.9800
12:109714897:GG:G	donor_gain	0.9800

AlphaMissense

2875 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:109768066:T:C	L46P	0.999
12:109768078:C:A	A50D	0.998
12:109768114:T:C	I62T	0.998
12:109769195:G:C	K422N	0.998
12:109769195:G:T	K422N	0.998
12:109768108:T:A	I60N	0.997
12:109768114:T:G	I62S	0.997
12:109768116:T:C	F63L	0.997
12:109768117:T:C	F63S	0.997
12:109768117:T:G	F63C	0.997
12:109768118:C:A	F63L	0.997
12:109768118:C:G	F63L	0.997
12:109769164:T:C	L412P	0.997
12:109768074:T:G	Y49D	0.996
12:109768077:G:C	A50P	0.996
12:109769142:A:C	S405R	0.996
12:109769144:C:A	S405R	0.996
12:109769144:C:G	S405R	0.996
12:109744156:T:C	C4R	0.995
12:109768066:T:A	L46Q	0.995
12:109768114:T:A	I62N	0.995
12:109768165:T:A	V79D	0.995
12:109768071:G:C	A48P	0.994
12:109768108:T:G	I60S	0.994
12:109768169:T:A	N80K	0.993
12:109768169:T:G	N80K	0.993
12:109744158:T:G	C4W	0.992
12:109768135:T:A	V69E	0.992
12:109768310:G:C	K127N	0.992
12:109768310:G:T	K127N	0.992

dbSNP variants (sampled 300 via entrez): RS1000143821 (12:109734730 G>A,C), RS1000178989 (12:109740251 G>A), RS1000179986 (12:109738010 A>G), RS1000206058 (12:109743448 G>A), RS1000294980 (12:109726496 A>G), RS1000318003 (12:109737716 G>A,T), RS1000333314 (12:109757286 T>C), RS1000377101 (12:109732443 G>A), RS1000408860 (12:109743468 G>A), RS1000437737 (12:109746095 T>G), RS1000476109 (12:109734678 A>G), RS1000514342 (12:109739194 T>C), RS1000583533 (12:109739386 C>T), RS1000650177 (12:109738976 C>A,G,T), RS1000829292 (12:109733482 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST005974_9	Neutrophil count	6.000000e-09
GCST005999_21	Aspartate aminotransferase levels	3.000000e-08
GCST006005_19	High density lipoprotein cholesterol levels	5.000000e-18
GCST008151_13	Waist circumference	6.000000e-06
GCST008160_58	Waist circumference	6.000000e-06
GCST012020_189	Serum metabolite levels	2.000000e-11
GCST012021_114	Serum metabolite levels	2.000000e-11
GCST90014268_27	Cataracts	1.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count
EFO:0004736	aspartate aminotransferase measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	increases expression	3
Valproic Acid	affects expression, increases expression, increases methylation	3
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	affects cotreatment, decreases expression	2
belinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Estradiol	affects binding, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, decreases expression	1
licochalcone B	increases expression	1
jinfukang	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Atrazine	increases expression	1

Clinical trials (associated diseases)

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