FAM227A

Summary

FAM227A (family with sequence similarity 227 member A, HGNC:44197) is a protein-coding gene on chromosome 22q13.1, encoding Protein FAM227A (F5H4B4).

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 93 total
• MANE Select transcript: NM_001013647

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44197
Approved symbol	FAM227A
Name	family with sequence similarity 227 member A
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000184949
Ensembl biotype	protein_coding
Entrez	646851

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding_CDS_not_defined, 3 protein_coding, 2 retained_intron

ENST00000355830, ENST00000424706, ENST00000484582, ENST00000490082, ENST00000535113, ENST00000540952, ENST00000541689, ENST00000543295, ENST00000543828, ENST00000544346, ENST00000608409

RefSeq mRNA: 4 — MANE Select: NM_001013647 NM_001013647, NM_001291030, NM_001384270, NM_001384271

CCDS: CCDS93164

Canonical transcript exons

ENST00000535113 — 17 exons

Exon	Start	End
ENSE00002259648	38578118	38586199
ENSE00002261298	38591435	38591540
ENSE00003479253	38639655	38639724
ENSE00003500476	38636451	38636597
ENSE00003502278	38623172	38623279
ENSE00003513808	38650027	38650262
ENSE00003531423	38620212	38620291
ENSE00003554745	38605254	38605348
ENSE00003571280	38626180	38626303
ENSE00003572340	38597204	38597356
ENSE00003604883	38628834	38628935
ENSE00003607556	38628238	38628342
ENSE00003642881	38638746	38638822
ENSE00003646404	38599764	38599921
ENSE00003663355	38607389	38607476
ENSE00003691402	38645563	38645645
ENSE00003921502	38656120	38656392

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 87.86.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6136 / max 59.9357, expressed in 731 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194201	0.6492	360
194199	0.5384	191
194200	0.4038	194
194198	0.0221	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	87.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.59	gold quality
right testis	UBERON:0004534	79.12	gold quality
left testis	UBERON:0004533	78.95	gold quality
testis	UBERON:0000473	78.81	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.00	gold quality
ventricular zone	UBERON:0003053	74.37	gold quality
pituitary gland	UBERON:0000007	73.38	gold quality
stromal cell of endometrium	CL:0002255	73.15	gold quality
adenohypophysis	UBERON:0002196	72.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.03	gold quality
cortical plate	UBERON:0005343	71.69	gold quality
sural nerve	UBERON:0015488	71.16	gold quality
fallopian tube	UBERON:0003889	70.75	gold quality
endometrium	UBERON:0001295	70.37	gold quality
ganglionic eminence	UBERON:0004023	70.15	gold quality
corpus callosum	UBERON:0002336	68.25	gold quality
superior frontal gyrus	UBERON:0002661	65.80	gold quality
thyroid gland	UBERON:0002046	65.17	gold quality
left lobe of thyroid gland	UBERON:0001120	64.88	gold quality
right lobe of thyroid gland	UBERON:0001119	64.76	gold quality
colonic epithelium	UBERON:0000397	64.57	silver quality
caudate nucleus	UBERON:0001873	64.02	gold quality
cortex of kidney	UBERON:0001225	63.66	gold quality
hypothalamus	UBERON:0001898	63.58	gold quality
metanephros cortex	UBERON:0010533	63.13	gold quality
nucleus accumbens	UBERON:0001882	62.95	gold quality
left uterine tube	UBERON:0001303	62.45	gold quality
kidney	UBERON:0002113	62.43	gold quality
endocervix	UBERON:0000458	62.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

249 targeting FAM227A, 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-3163	100.00	77.23	8605
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fam227a	ENSMUSG00000042564
rattus_norvegicus	Fam227a	ENSRNOG00000021795

Protein

Protein identifiers

Protein FAM227A — F5H4B4 (reviewed: F5H4B4)

All UniProt accessions (3): F5H4B4, A0A0A0MRD0, A0A2R8YCE3

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the FAM227 family.

Isoforms (2)

UniProt ID	Names	Canonical?
F5H4B4-1	1	yes
F5H4B4-2	2

RefSeq proteins (4): NP_001013669, NP_001277959, NP_001371199, NP_001371200 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029417	FAM227	Family

Pfam: PF14922

UniProt features (15 total): compositionally biased region 4, region of interest 3, modified residue 3, splice variant 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-F5H4B4-F1	65.23	0.14

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 (3): 349, 343, 348

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 64 (showing top): chr22q13, ZWANG_DOWN_BY_2ND_EGF_PULSE, ASH1L_TARGET_GENES, BANP_TARGET_GENES, E2F2_TARGET_GENES, FOXJ2_TARGET_GENES, HHEX_TARGET_GENES, MAFG_TARGET_GENES, NKX2_2_TARGET_GENES, SKIL_TARGET_GENES, TEAD2_TARGET_GENES, CASP8AP2_TARGET_GENES, ZIM3_TARGET_GENES, MIR1297, MIR4666A_3P

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

204 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM227A	PRSS38	A1L453	527
FAM227A	SLC35E4	Q6ICL7	507
FAM227A	ITPRIPL2	Q3MIP1	447
FAM227A	HSBP1L1	C9JCN9	438
FAM227A	CFAP70	Q5T0N1	394
FAM227A	SUSD5	O60279	378
FAM227A	TAFA2	Q8N3H0	371
FAM227A	COQ10B	Q9H8M1	357
FAM227A	EEIG1	Q5T9C2	354
FAM227A	SUN2	Q9UH99	348
FAM227A	CFAP251	Q8TBY9	338
FAM227A	TMSB15A	P0CG34	317
FAM227A	TAFA5	Q7Z5A7	316
FAM227A	PRTG	Q2VWP7	312
FAM227A	DIP2C	Q9Y2E4	311

IntAct

2 interactions, top by confidence:

A	B	Type	Score
FAM227A	ARPC1B	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (2): ARPC1B (Proximity Label-MS), FAM227A (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0R4I9Y1, A0A0R4IBK5, A2ARZ3, A5WUT8, A6NKT7, A7S7F2, E9Q3L2, E9Q555, F1QB81, F5H4B4, H2QII6, O08662, O14715, O15050, O43310, P0DJD0, P0DJD1, P13864, P42356, P49792, Q06190, Q0V9S3, Q0VF22, Q16533, Q1LVQ2, Q24K09, Q2T9I9, Q4R6W9, Q4V847, Q5U228, Q63HN8, Q65Z40, Q6NU22, Q6NU51, Q7TPV2, Q7Z3J3, Q80TA9, Q811D2, Q86Y13, Q921I6

Diamond homologs: F5H4B4, Q4R7D5, Q6AXP3, Q9D518, Q96M60

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3351 predictions. Top by Δscore:

Variant	Effect	Δscore
22:38586100:T:TA	donor_gain	1.0000
22:38591414:A:AC	donor_gain	1.0000
22:38591432:T:TA	donor_gain	1.0000
22:38623170:AC:A	donor_gain	1.0000
22:38623171:CC:C	donor_gain	1.0000
22:38636445:CCTCA:C	donor_loss	1.0000
22:38636447:TCA:T	donor_loss	1.0000
22:38636448:CACCT:C	donor_loss	1.0000
22:38636449:A:T	donor_loss	1.0000
22:38636450:C:CA	donor_loss	1.0000
22:38636594:TTTT:T	acceptor_gain	1.0000
22:38636595:TTT:T	acceptor_gain	1.0000
22:38636596:TT:T	acceptor_gain	1.0000
22:38636598:C:CC	acceptor_gain	1.0000
22:38636604:C:CT	acceptor_gain	1.0000
22:38636605:A:T	acceptor_gain	1.0000
22:38638744:AC:A	donor_gain	1.0000
22:38638745:CC:C	donor_gain	1.0000
22:38638818:CTTGA:C	acceptor_gain	1.0000
22:38638819:TTGA:T	acceptor_gain	1.0000
22:38638823:C:CC	acceptor_gain	1.0000
22:38650051:T:TA	donor_gain	1.0000
22:38586045:A:AC	donor_gain	0.9900
22:38586045:ATTTT:A	donor_gain	0.9900
22:38586046:T:C	donor_gain	0.9900
22:38591359:A:AC	donor_gain	0.9900
22:38591360:C:CC	donor_gain	0.9900
22:38591415:A:C	donor_gain	0.9900
22:38591439:G:C	donor_gain	0.9900
22:38591457:T:TA	donor_gain	0.9900

AlphaMissense

3806 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:38626265:G:C	S255R	0.996
22:38626265:G:T	S255R	0.996
22:38626267:T:G	S255R	0.996
22:38599859:G:C	S428R	0.993
22:38599859:G:T	S428R	0.993
22:38599861:T:G	S428R	0.993
22:38626189:A:G	W281R	0.992
22:38626189:A:T	W281R	0.992
22:38628864:G:C	S197R	0.992
22:38628864:G:T	S197R	0.992
22:38628866:T:G	S197R	0.992
22:38626250:A:C	F260L	0.989
22:38626250:A:T	F260L	0.989
22:38626252:A:G	F260L	0.989
22:38623247:A:G	W295R	0.988
22:38623247:A:T	W295R	0.988
22:38628857:A:G	W200R	0.987
22:38628857:A:T	W200R	0.987
22:38628861:A:C	F198L	0.985
22:38628861:A:T	F198L	0.985
22:38628863:A:G	F198L	0.985
22:38626217:C:A	K271N	0.983
22:38626217:C:G	K271N	0.983
22:38626262:G:C	F256L	0.983
22:38626262:G:T	F256L	0.983
22:38626264:A:G	F256L	0.983
22:38626220:G:C	F270L	0.982
22:38626220:G:T	F270L	0.982
22:38626222:A:G	F270L	0.982
22:38628860:A:G	W199R	0.982

dbSNP variants (sampled 300 via entrez): RS1000014531 (22:38632237 G>A), RS1000087048 (22:38639456 G>A), RS1000090830 (22:38598887 C>T), RS1000117809 (22:38615761 T>A), RS1000147590 (22:38622465 G>A), RS1000193868 (22:38653913 G>A,T), RS1000199509 (22:38650931 C>T), RS1000201548 (22:38643309 C>G), RS1000275379 (22:38615487 A>G), RS1000299587 (22:38598509 A>T), RS1000343023 (22:38621710 C>T), RS1000379090 (22:38616658 C>G), RS1000403443 (22:38647925 C>T), RS1000443881 (22:38627816 C>T), RS1000464455 (22:38588944 G>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

9 associations (top):

Study	Trait	p-value
GCST003818_40	Resting heart rate	5.000000e-16
GCST006019_42	Gamma glutamyl transferase levels	3.000000e-10
GCST006979_828	Heel bone mineral density	6.000000e-34
GCST011349_32	Gamma glutamyl transferase levels	6.000000e-11
GCST90002384_505	Hemoglobin	2.000000e-11
GCST90002390_329	Mean corpuscular hemoglobin	3.000000e-14
GCST90002392_224	Mean corpuscular volume	1.000000e-19
GCST90002397_608	Mean spheric corpuscular volume	4.000000e-17
GCST90013406_211	Liver enzyme levels (alkaline phosphatase)	2.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0009270	heel bone mineral density
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
trichostatin A	affects expression	1
sodium arsenite	decreases expression	1
2-palmitoylglycerol	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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