FAM221A

Summary

FAM221A (family with sequence similarity 221 member A, HGNC:27977) is a protein-coding gene on chromosome 7p15.3, encoding Protein FAM221A (A4D161).

At a glance

• Clinical variants (ClinVar): 72 total
• MANE Select transcript: NM_199136

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27977
Approved symbol	FAM221A
Name	family with sequence similarity 221 member A
Location	7p15.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ45875, MGC72075, DKFZp686F0810
Ensembl gene	ENSG00000188732
Ensembl biotype	protein_coding
Entrez	340277

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 23 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000344962, ENST00000409192, ENST00000409653, ENST00000409994, ENST00000429719, ENST00000446234, ENST00000462546, ENST00000483090, ENST00000871250, ENST00000871251, ENST00000871252, ENST00000871253, ENST00000871254, ENST00000871255, ENST00000871256, ENST00000871257, ENST00000929833, ENST00000929834, ENST00000929835, ENST00000929836, ENST00000929837, ENST00000929838, ENST00000929839, ENST00000929840, ENST00000929841, ENST00000929842, ENST00000929843

RefSeq mRNA: 4 — MANE Select: NM_199136 NM_001127364, NM_001127365, NM_001300932, NM_199136

CCDS: CCDS47561, CCDS47562, CCDS5385, CCDS75570

Canonical transcript exons

ENST00000344962 — 7 exons

Exon	Start	End
ENSE00003459641	23698192	23698299
ENSE00003499021	23702096	23702650
ENSE00003518115	23700786	23700868
ENSE00003591795	23691390	23691596
ENSE00003657651	23689269	23689459
ENSE00003667589	23684499	23684672
ENSE00003845707	23680199	23680283

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 93.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4035 / max 100.1143, expressed in 1119 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77681	6.4035	1119

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	93.93	silver quality
bronchial epithelial cell	CL:0002328	93.41	gold quality
pigmented layer of retina	UBERON:0001782	92.66	gold quality
bronchus	UBERON:0002185	92.14	gold quality
germinal epithelium of ovary	UBERON:0001304	92.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.09	gold quality
oviduct epithelium	UBERON:0004804	92.07	gold quality
right uterine tube	UBERON:0001302	92.05	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.12	gold quality
body of pancreas	UBERON:0001150	90.78	gold quality
epithelial cell of pancreas	CL:0000083	90.43	silver quality
mucosa of paranasal sinus	UBERON:0005030	90.20	gold quality
spinal cord	UBERON:0002240	89.70	gold quality
Brodmann (1909) area 46	UBERON:0006483	88.09	gold quality
lower esophagus mucosa	UBERON:0035834	87.71	gold quality
pancreas	UBERON:0001264	87.64	gold quality
body of stomach	UBERON:0001161	86.77	gold quality
ganglionic eminence	UBERON:0004023	86.53	gold quality
hypothalamus	UBERON:0001898	86.12	gold quality
substantia nigra	UBERON:0002038	85.28	gold quality
Ammon’s horn	UBERON:0001954	85.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.12	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.87	gold quality
left testis	UBERON:0004533	84.84	gold quality
right testis	UBERON:0004534	84.82	gold quality
putamen	UBERON:0001874	84.76	gold quality
stomach	UBERON:0000945	84.67	gold quality
anterior cingulate cortex	UBERON:0009835	84.61	gold quality
duodenum	UBERON:0002114	84.56	gold quality
amygdala	UBERON:0001876	84.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting FAM221A, 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-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam221a	ENSDARG00000027599
mus_musculus	Fam221a	ENSMUSG00000047115
rattus_norvegicus	Fam221a	ENSRNOG00000009447

Paralogs (1): FAM221B (ENSG00000204930)

Protein

Protein identifiers

Protein FAM221A — A4D161 (reviewed: A4D161)

All UniProt accessions (4): A4D161, B8ZZQ8, F8WCP2, F8WCP3

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the FAM221 family.

Isoforms (3)

UniProt ID	Names	Canonical?
A4D161-1	1	yes
A4D161-2	2
A4D161-3	3

RefSeq proteins (4): NP_001120836, NP_001120837, NP_001287861, NP_954587* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026755	Fam221a/b	Family

Pfam: PF14753

UniProt features (11 total): sequence variant 5, splice variant 2, chain 1, region of interest 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A4D161-F1	84.09	0.57

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 74 (showing top): GATA3_01, OSMAN_BLADDER_CANCER_DN, BOYLAN_MULTIPLE_MYELOMA_PCA3_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN, NOUSHMEHR_GBM_SILENCED_BY_METHYLATION, FEVR_CTNNB1_TARGETS_UP, PEDRIOLI_MIR31_TARGETS_UP, LIM_MAMMARY_STEM_CELL_DN, FOXD2_TARGET_GENES, HOXB4_TARGET_GENES, LCORL_TARGET_GENES, ZBTB12_TARGET_GENES, GSE10240_CTRL_VS_IL17_AND_IL22_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_UP, MIR520D_5P, MIR524_5P

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

340 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM221A	OR6T1	Q8NGN1	580
FAM221A	OR51M1	Q9H341	571
FAM221A	FAM219B	Q5XKK7	479
FAM221A	PGCKA1	Q8IY42	447
FAM221A	HEATR9	A2RTY3	445
FAM221A	C17orf78	Q8N4C9	434
FAM221A	KATNBL1	Q9H079	418
FAM221A	AMZ1	Q400G9	401
FAM221A	UNC93A	Q86WB7	400
FAM221A	SPATS2	Q86XZ4	391
FAM221A	OR4D9	Q8NGE8	369
FAM221A	OR1L6	Q8NGR2	367
FAM221A	CCDC57	Q2TAC2	360
FAM221A	DIP2B	Q9P265	351
FAM221A	TEX22	C9J3V5	351

IntAct

61 interactions, top by confidence:

A	B	Type	Score
FAM221A	HOXA1	psi-mi:“MI:0915”(physical association)	0.670
FAM221A	NOTCH2NLC	psi-mi:“MI:0915”(physical association)	0.560
FAM221A	CYSRT1	psi-mi:“MI:0915”(physical association)	0.560
FAM221A	LHX3	psi-mi:“MI:0915”(physical association)	0.560
FAM221A	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.560
FAM221A	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
FAM221A	SUMO3	psi-mi:“MI:0915”(physical association)	0.560
FAM221A	ANKS1A	psi-mi:“MI:0915”(physical association)	0.560
FAM221A	PFDN5	psi-mi:“MI:0915”(physical association)	0.560
FAM221A	PRRG2	psi-mi:“MI:0915”(physical association)	0.560
FAM221A	ZNF417	psi-mi:“MI:0915”(physical association)	0.560
FAM221A	KRTAP4-11	psi-mi:“MI:0915”(physical association)	0.560
FAM221A	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.560
FAM221A	CDPF1	psi-mi:“MI:0915”(physical association)	0.560
FAM221A	DMWD	psi-mi:“MI:0915”(physical association)	0.560
FAM221A		psi-mi:“MI:0915”(physical association)	0.560
FAM221A	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
FAM221A	SNX2	psi-mi:“MI:0914”(association)	0.530
ECE1	FAM221A	psi-mi:“MI:0915”(physical association)	0.370
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (27): SNX5 (Affinity Capture-MS), SNX2 (Affinity Capture-MS), SNX6 (Affinity Capture-MS), SNX6 (Affinity Capture-MS), SNX5 (Affinity Capture-MS), SNX2 (Affinity Capture-MS), FAM221A (Affinity Capture-RNA), FAM221A (Two-hybrid), FAM221A (Two-hybrid), FAM221A (Two-hybrid), FAM221A (Two-hybrid), FAM221A (Two-hybrid), FAM221A (Two-hybrid), FAM221A (Two-hybrid), FAM221A (Two-hybrid)

ESM2 similar proteins: A4D161, A6H7A8, E1BGQ2, O70524, O75391, P29084, P29540, P70445, Q14161, Q15650, Q28J59, Q2KJF9, Q2NL14, Q2VPL9, Q32LC9, Q32NC0, Q3ZK22, Q4V8D7, Q4VA36, Q5R595, Q5R802, Q5R9D9, Q5RFL7, Q5XI52, Q5ZJK1, Q66H91, Q6AY70, Q7TNE3, Q861R7, Q86UT8, Q8BND4, Q8BQR4, Q8BXK4, Q8C790, Q8IWR0, Q8K2I9, Q8NFZ0, Q8VDD9, Q8WWQ0, Q922H9

Diamond homologs: A4D161, Q28J59, Q2VPL9, Q4V8D7, Q8C790, A6H8Z2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1242 predictions. Top by Δscore:

Variant	Effect	Δscore
7:23680281:G:GT	donor_gain	1.0000
7:23680282:AGGTG:A	donor_loss	1.0000
7:23689264:TTTA:T	acceptor_loss	1.0000
7:23689267:A:AG	acceptor_gain	1.0000
7:23689267:AG:A	acceptor_gain	1.0000
7:23689268:G:GA	acceptor_gain	1.0000
7:23689268:GG:G	acceptor_gain	1.0000
7:23689268:GGT:G	acceptor_gain	1.0000
7:23689268:GGTA:G	acceptor_gain	1.0000
7:23689268:GGTAT:G	acceptor_gain	1.0000
7:23689455:TACAT:T	donor_gain	1.0000
7:23689456:ACAT:A	donor_gain	1.0000
7:23689456:ACATG:A	donor_loss	1.0000
7:23689457:CAT:C	donor_gain	1.0000
7:23689458:AT:A	donor_gain	1.0000
7:23689459:TG:T	donor_loss	1.0000
7:23689460:G:GG	donor_gain	1.0000
7:23691387:CAGGT:C	acceptor_loss	1.0000
7:23691592:GATTG:G	donor_gain	1.0000
7:23700785:GTA:G	acceptor_gain	1.0000
7:23700864:A:T	donor_gain	1.0000
7:23680259:TGGAC:T	donor_gain	0.9900
7:23680260:GGACG:G	donor_gain	0.9900
7:23680280:GGAG:G	donor_gain	0.9900
7:23680281:GAG:G	donor_gain	0.9900
7:23684498:GAATT:G	acceptor_gain	0.9900
7:23691594:TTGG:T	donor_loss	0.9900
7:23691597:GTAAG:G	donor_loss	0.9900
7:23691598:T:TC	donor_loss	0.9900
7:23698296:GATG:G	donor_gain	0.9900

AlphaMissense

1936 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:23691407:T:C	F150L	0.975
7:23691409:C:A	F150L	0.975
7:23691409:C:G	F150L	0.975
7:23691413:A:C	S152R	0.958
7:23691415:C:A	S152R	0.958
7:23691415:C:G	S152R	0.958
7:23684605:T:A	W58R	0.948
7:23684605:T:C	W58R	0.948
7:23684596:T:C	F55L	0.937
7:23684598:T:A	F55L	0.937
7:23684598:T:G	F55L	0.937
7:23680276:T:C	Y20H	0.933
7:23691548:T:C	F197L	0.926
7:23691550:C:A	F197L	0.926
7:23691550:C:G	F197L	0.926
7:23691408:T:C	F150S	0.925
7:23684602:A:C	S57R	0.923
7:23684604:C:A	S57R	0.923
7:23684604:C:G	S57R	0.923
7:23684659:T:C	F76L	0.918
7:23684661:T:A	F76L	0.918
7:23684661:T:G	F76L	0.918
7:23689270:T:G	Y81D	0.915
7:23684559:A:C	K42N	0.914
7:23684559:A:T	K42N	0.914
7:23689279:C:G	H84D	0.910
7:23691419:T:C	F154L	0.907
7:23691421:C:A	F154L	0.907
7:23691421:C:G	F154L	0.907
7:23684504:T:A	V24D	0.903

dbSNP variants (sampled 300 via entrez): RS1000010422 (7:23682221 G>A), RS1000023013 (7:23696431 G>A), RS1000080029 (7:23683754 T>C), RS1000117240 (7:23688598 C>T), RS1000354543 (7:23702360 T>C), RS1000490949 (7:23688789 A>C,G), RS1000548370 (7:23691465 T>C), RS1000928395 (7:23691653 A>G), RS1000934129 (7:23696425 T>C), RS1000963789 (7:23696214 T>C), RS1000979055 (7:23684000 C>T), RS1001010126 (7:23683708 C>A), RS1001182909 (7:23679107 G>C), RS1001288787 (7:23688825 G>A), RS1001454583 (7:23701812 T>A)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Valproic Acid	affects cotreatment, decreases expression	3
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
urushiol	increases expression	1
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
beta-lapachone	increases expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
nickel sulfate	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Fonofos	increases methylation	1
Estradiol	affects cotreatment, decreases expression	1
Niclosamide	increases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Vanadates	decreases expression	1

Clinical trials (associated diseases)

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