FAM227B

Summary

FAM227B (family with sequence similarity 227 member B, HGNC:26543) is a protein-coding gene on chromosome 15q21.2, encoding Protein FAM227B (Q96M60).

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 124 total
• MANE Select transcript: NM_152647

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26543
Approved symbol	FAM227B
Name	family with sequence similarity 227 member B
Location	15q21.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32800
Ensembl gene	ENSG00000166262
Ensembl biotype	protein_coding
Entrez	196951

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 8 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000299338, ENST00000557892, ENST00000558579, ENST00000558594, ENST00000558615, ENST00000558862, ENST00000559351, ENST00000559573, ENST00000559905, ENST00000560246, ENST00000560557, ENST00000561064, ENST00000561116, ENST00000561319, ENST00000968443, ENST00000968444

RefSeq mRNA: 2 — MANE Select: NM_152647 NM_001330293, NM_152647

CCDS: CCDS32237, CCDS81880

Canonical transcript exons

ENST00000299338 — 16 exons

Exon	Start	End
ENSE00001101519	49541680	49541806
ENSE00001101530	49568245	49568346
ENSE00001363504	49575011	49575109
ENSE00001611442	49335419	49335496
ENSE00001670437	49367448	49367608
ENSE00002556968	49620700	49620818
ENSE00002568101	49326970	49328675
ENSE00002712073	49508211	49508348
ENSE00003465675	49577629	49577664
ENSE00003492889	49371302	49371399
ENSE00003514590	49611215	49611268
ENSE00003546155	49331780	49331849
ENSE00003611331	49588016	49588083
ENSE00003614479	49615121	49615243
ENSE00003666805	49589776	49590007
ENSE00003789912	49576741	49576845

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 89.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.6780 / max 91.0908, expressed in 1484 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149819	2.8429	1223
149821	0.5775	314
149820	0.5724	333
149818	0.4499	226
149822	0.2353	107

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.18	gold quality
buccal mucosa cell	CL:0002336	87.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.47	gold quality
right uterine tube	UBERON:0001302	86.39	gold quality
calcaneal tendon	UBERON:0003701	85.64	gold quality
left testis	UBERON:0004533	85.31	gold quality
right testis	UBERON:0004534	84.66	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.95	gold quality
muscle of leg	UBERON:0001383	83.84	gold quality
gastrocnemius	UBERON:0001388	83.78	gold quality
testis	UBERON:0000473	83.38	gold quality
islet of Langerhans	UBERON:0000006	83.08	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.74	gold quality
left ovary	UBERON:0002119	82.48	gold quality
right ovary	UBERON:0002118	81.90	gold quality
tibial nerve	UBERON:0001323	81.28	gold quality
adrenal tissue	UBERON:0018303	81.27	gold quality
adenohypophysis	UBERON:0002196	81.24	gold quality
right atrium auricular region	UBERON:0006631	81.04	gold quality
right adrenal gland	UBERON:0001233	80.90	gold quality
endocervix	UBERON:0000458	80.87	gold quality
body of pancreas	UBERON:0001150	80.58	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.55	gold quality
heart left ventricle	UBERON:0002084	80.28	gold quality
right adrenal gland cortex	UBERON:0035827	80.14	gold quality
left adrenal gland	UBERON:0001234	80.07	gold quality
body of uterus	UBERON:0009853	80.05	gold quality
cardiac atrium	UBERON:0002081	80.01	gold quality
left adrenal gland cortex	UBERON:0035825	79.84	gold quality
pancreas	UBERON:0001264	79.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.62
E-MTAB-7303	no	172.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting FAM227B, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-219A-2-3P	98.62	68.78	797
HSA-MIR-5585-3P	98.25	67.41	941
HSA-MIR-1255B-2-3P	97.80	67.04	880
HSA-MIR-4790-3P	96.63	67.08	806
HSA-MIR-675-3P	95.77	69.27	675
HSA-MIR-5009-5P	94.82	63.89	775
HSA-MIR-8058	94.76	63.41	632
HSA-MIR-5186	94.63	66.76	627
HSA-MIR-1269A	92.75	64.61	542
HSA-MIR-1269B	92.75	64.73	538

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fam227b	ENSMUSG00000027209
rattus_norvegicus	Fam227b	ENSRNOG00000037124

Protein

Protein identifiers

Protein FAM227B — Q96M60 (reviewed: Q96M60)

All UniProt accessions (6): H0YK12, H0YLX5, H0YMU4, H0YMX9, H0YNN2, Q96M60

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the FAM227 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96M60-1	1	yes
Q96M60-2	2

RefSeq proteins (2): NP_001317222, NP_689860* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029417	FAM227	Family

Pfam: PF14922

UniProt features (7 total): region of interest 2, splice variant 2, chain 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96M60-F1	71.40	0.13

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 92 (showing top): AACWWCAANK_UNKNOWN, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, PR_Q2, LEE_BMP2_TARGETS_DN, ALKBH3_TARGET_GENES, ARNT2_TARGET_GENES, BARX1_TARGET_GENES, CEBPZ_TARGET_GENES, CHAF1B_TARGET_GENES, DLX4_TARGET_GENES, FOXJ2_TARGET_GENES, GLI3_TARGET_GENES, GLI4_TARGET_GENES, HES2_TARGET_GENES, HMG20B_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

126 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM227B	LRRIQ3	A6PVS8	620
FAM227B	VXN	Q8TAG6	615
FAM227B	RNF144A	P50876	560
FAM227B	TMEM126B	Q8IUX1	515
FAM227B	KIFC3	Q9BVG8	515
FAM227B	FPGT	O14772	507
FAM227B	NOL4L	Q96MY1	499
FAM227B	CYRIA	Q9H0Q0	496
FAM227B	CFAP99	D6REC4	480
FAM227B	ROPN1L	Q96C74	463
FAM227B	XPO4	Q9C0E2	457
FAM227B	RAPGEF5	Q92565	449
FAM227B	KIF2B	Q8N4N8	444
FAM227B	CLSTN2	Q9H4D0	421
FAM227B	FOXI1	Q12951	381

IntAct

2 interactions, top by confidence:

A	B	Type	Score
FAM227B	NME2P1	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): FAM227B (Affinity Capture-MS), CALML3 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), PPL (Affinity Capture-MS), EPPK1 (Affinity Capture-MS), VPS28 (Affinity Capture-MS), NME2P1 (Affinity Capture-MS), TYMP (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), HIST2H2AC (Affinity Capture-MS), EVPL (Affinity Capture-MS), ACTB (Affinity Capture-MS), SERPINA3 (Affinity Capture-MS), SERPINB5 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVH7, A6PVS8, A8DZJ1, A9Q751, D3ZSP7, D4AEC2, Q08AD1, Q08CX2, Q14DL3, Q2T9P0, Q2TA00, Q32KQ1, Q3UZ57, Q3V0J4, Q4G0U5, Q4R7B1, Q4R7Z7, Q5S003, Q5SUV2, Q5T1B0, Q5ZLS8, Q63164, Q66HC0, Q69CM7, Q6AXP3, Q6AYL8, Q6IRN6, Q6NXP0, Q6Q759, Q80X60, Q86WZ0, Q8C1B1, Q8C4J0, Q8C636, Q8CDN1, Q8CDU5, Q8IWF9, Q8N7B9, Q8N7U6, Q8ND61

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4575 predictions. Top by Δscore:

Variant	Effect	Δscore
15:49371298:AAACC:A	donor_loss	1.0000
15:49371299:AACCT:A	donor_loss	1.0000
15:49371301:C:CG	donor_loss	1.0000
15:49371333:T:TA	donor_gain	1.0000
15:49371397:TAC:T	acceptor_gain	1.0000
15:49371399:CCTA:C	acceptor_loss	1.0000
15:49371400:C:CC	acceptor_gain	1.0000
15:49371400:CTAAA:C	acceptor_loss	1.0000
15:49371406:C:CT	acceptor_gain	1.0000
15:49483136:T:A	acceptor_gain	1.0000
15:49483138:T:TA	acceptor_gain	1.0000
15:49483147:GCA:G	acceptor_loss	1.0000
15:49483148:CA:C	acceptor_loss	1.0000
15:49483149:A:AG	acceptor_gain	1.0000
15:49483150:G:GC	acceptor_gain	1.0000
15:49483150:GA:G	acceptor_gain	1.0000
15:49483150:GAT:G	acceptor_gain	1.0000
15:49483150:GATA:G	acceptor_gain	1.0000
15:49483150:GATAT:G	acceptor_gain	1.0000
15:49483202:TGGA:T	donor_gain	1.0000
15:49483234:G:GT	donor_gain	1.0000
15:49483235:A:T	donor_gain	1.0000
15:49483250:CAAAG:C	donor_loss	1.0000
15:49483251:AAAGG:A	donor_loss	1.0000
15:49483252:AAGGT:A	donor_loss	1.0000
15:49483253:AGGT:A	donor_loss	1.0000
15:49483256:T:G	donor_loss	1.0000
15:49484305:AACAG:A	acceptor_loss	1.0000
15:49484306:ACAGA:A	acceptor_loss	1.0000
15:49484308:A:AG	acceptor_gain	1.0000

AlphaMissense

3383 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:49367546:A:C	S391R	0.992
15:49367546:A:T	S391R	0.992
15:49367548:T:G	S391R	0.992
15:49541689:A:G	W289R	0.992
15:49541689:A:T	W289R	0.992
15:49541782:C:G	A258P	0.990
15:49575034:A:G	W208R	0.988
15:49575034:A:T	W208R	0.988
15:49541758:C:G	A266P	0.986
15:49575038:A:C	F206L	0.986
15:49575038:A:T	F206L	0.986
15:49575040:A:G	F206L	0.986
15:49541753:A:C	F267L	0.985
15:49541753:A:T	F267L	0.985
15:49541755:A:G	F267L	0.985
15:49508316:A:G	W303R	0.984
15:49508316:A:T	W303R	0.984
15:49575037:A:G	W207R	0.984
15:49575037:A:T	W207R	0.984
15:49541717:T:A	K279N	0.981
15:49541717:T:G	K279N	0.981
15:49541709:A:G	L282P	0.980
15:49335459:C:G	A437P	0.979
15:49575014:A:C	F214L	0.979
15:49575014:A:T	F214L	0.979
15:49575016:A:G	F214L	0.979
15:49611233:G:C	F29L	0.979
15:49611233:G:T	F29L	0.979
15:49611235:A:G	F29L	0.979
15:49541720:A:C	F278L	0.978

dbSNP variants (sampled 300 via entrez): RS1000008209 (15:49358636 C>G,T), RS1000020066 (15:49577400 T>A,C), RS1000028952 (15:49453212 T>A), RS1000036230 (15:49328215 T>A), RS1000044680 (15:49491848 G>A), RS1000060000 (15:49452837 G>A), RS1000063705 (15:49357433 A>G), RS1000069336 (15:49377372 G>A), RS1000073913 (15:49531321 T>C), RS1000083641 (15:49432021 G>A), RS1000083828 (15:49400830 C>T), RS1000087668 (15:49583613 T>C), RS1000095653 (15:49446566 T>C), RS1000099087 (15:49424129 G>A), RS1000136448 (15:49400367 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): autoinflammatory syndrome (MONDO:0019751)

Orphanet (1): Autoinflammatory syndrome (Orphanet:93665)

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001069_2	Thyroid volume	3.000000e-13
GCST001069_6	Thyroid volume	1.000000e-12
GCST004744_35	Lung adenocarcinoma	6.000000e-10
GCST004744_39	Lung adenocarcinoma	2.000000e-09
GCST007430_57	Peak expiratory flow	1.000000e-09
GCST007431_24	Lung function (FEV1/FVC)	3.000000e-27
GCST007432_55	FEV1	9.000000e-16
GCST009391_952	Metabolite levels	4.000000e-06
GCST010243_243	Apolipoprotein B levels	7.000000e-10
GCST010245_36	LDL cholesterol levels	6.000000e-09
GCST010653_86	Thyroid stimulating hormone levels	8.000000e-44
GCST90011899_155	Aspartate aminotransferase levels	9.000000e-09
GCST90013407_156	Liver enzyme levels (gamma-glutamyl transferase)	2.000000e-12

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume
EFO:0010443	triacylglycerol 58:9 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Valproic Acid	decreases methylation, decreases expression	2
GSK-J4	decreases expression	1
Esketamine	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
pentanal	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
dorsomorphin	decreases expression, affects cotreatment	1
Acetaminophen	increases expression	1
Estradiol	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Malathion	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00442182	PHASE2	UNKNOWN	The Efficacy and Safety of ITF2357 in AIS
NCT00887939	Not specified	COMPLETED	Pathogenesis of Physical Induced Urticarial Syndromes
NCT03510442	Not specified	RECRUITING	Natural History, Genetics, and Pathophysiology of Systemic Juvenile Idiopathic Arthritis, Adult-Onset Still’s Disease, and Related Conditions
NCT06248957	Not specified	RECRUITING	SYSTEMS-LEVEL ANALYSES OF IMMUNE DYSREGULATION