FAM228B

Summary

FAM228B (family with sequence similarity 228 member B, HGNC:24736) is a protein-coding gene on chromosome 2p23.3, encoding Protein FAM228B (P0C875).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 120 total
• MANE Select transcript: NM_001145710

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24736
Approved symbol	FAM228B
Name	family with sequence similarity 228 member B
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000219626
Ensembl biotype	protein_coding
Entrez	375190

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 22 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000460686, ENST00000461972, ENST00000469867, ENST00000486967, ENST00000611138, ENST00000611917, ENST00000613899, ENST00000615135, ENST00000615575, ENST00000897482, ENST00000897483, ENST00000897484, ENST00000897485, ENST00000897486, ENST00000920459, ENST00000920460, ENST00000920461, ENST00000971748, ENST00000971749, ENST00000971750, ENST00000971751, ENST00000971752, ENST00000971753, ENST00000971754, ENST00000971755, ENST00000971756, ENST00000971757, ENST00000971758

RefSeq mRNA: 2 — MANE Select: NM_001145710 NM_001145710, NM_001291328

CCDS: CCDS74491, CCDS77387

Canonical transcript exons

ENST00000615575 — 11 exons

Exon	Start	End
ENSE00003719894	24146930	24147086
ENSE00003722009	24123469	24123533
ENSE00003725769	24139370	24139450
ENSE00003728804	24164198	24164335
ENSE00003731376	24167627	24167683
ENSE00003735198	24161506	24161613
ENSE00003737542	24137909	24138100
ENSE00003746414	24169356	24169638
ENSE00003749945	24124330	24124460
ENSE00003750708	24135119	24135187
ENSE00003754782	24146748	24146835

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 96.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.2001 / max 108.5483, expressed in 1587 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19172	2.9194	1320
19173	1.4702	799
19171	0.3364	162
19170	0.1787	84
202112	0.1487	51
19174	0.1469	47

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.78	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.83	gold quality
left testis	UBERON:0004533	94.77	gold quality
right testis	UBERON:0004534	94.77	gold quality
amygdala	UBERON:0001876	94.32	gold quality
spinal cord	UBERON:0002240	94.25	gold quality
hypothalamus	UBERON:0001898	94.03	gold quality
adenohypophysis	UBERON:0002196	93.93	gold quality
pituitary gland	UBERON:0000007	93.89	gold quality
lateral globus pallidus	UBERON:0002476	93.85	gold quality
corpus callosum	UBERON:0002336	93.51	gold quality
right uterine tube	UBERON:0001302	93.32	gold quality
substantia nigra	UBERON:0002038	93.22	gold quality
testis	UBERON:0000473	93.01	gold quality
anterior cingulate cortex	UBERON:0009835	92.85	gold quality
midbrain	UBERON:0001891	92.50	gold quality
nucleus accumbens	UBERON:0001882	92.49	gold quality
putamen	UBERON:0001874	92.43	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.37	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.37	gold quality
right frontal lobe	UBERON:0002810	92.21	gold quality
caudate nucleus	UBERON:0001873	92.18	gold quality
cerebellar hemisphere	UBERON:0002245	91.71	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.68	silver quality
cerebellar cortex	UBERON:0002129	91.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.65	gold quality
tibial nerve	UBERON:0001323	91.51	gold quality
tendon	UBERON:0000043	91.36	gold quality
tibial artery	UBERON:0007610	91.27	gold quality
popliteal artery	UBERON:0002250	91.26	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-6	yes	4008.06
E-MTAB-7381	no	107.31
E-MTAB-7606	no	54.48
E-ANND-3	no	4.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting FAM228B, 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-4776-3P	100.00	68.73	1340
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-942-3P	98.81	69.04	876
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-561-5P	98.25	68.13	1365
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-3620-3P	97.78	64.88	772
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-617	96.79	65.96	738

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam228a	ENSDARG00000042936
mus_musculus	Fam228b	ENSMUSG00000050545
rattus_norvegicus	Fam228b	ENSRNOG00000049615

Paralogs (1): FAM228A (ENSG00000186453)

Protein

Protein identifiers

Protein FAM228B — P0C875 (reviewed: P0C875)

All UniProt accessions (5): P0C875, A0A087WTY8, A0A087WVX1, A0A087WZM6, A0A087WZN6

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the FAM228 family.

RefSeq proteins (2): NP_001139182, NP_001278257 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR040046	FAM228	Family

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C875-F1	68.53	0.25

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 77 (showing top): BASAKI_YBX1_TARGETS_DN, ALKBH3_TARGET_GENES, CBX7_TARGET_GENES, DIDO1_TARGET_GENES, DLX4_TARGET_GENES, HES4_TARGET_GENES, HMG20B_TARGET_GENES, HOXB4_TARGET_GENES, ID2_TARGET_GENES, IRF5_TARGET_GENES, KAT2A_TARGET_GENES, NAB2_TARGET_GENES, PAX3_TARGET_GENES, RORA_TARGET_GENES, RYBP_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

334 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM228B	BET1L	Q9NYM9	591
FAM228B	MINDY4	Q4G0A6	455
FAM228B	TTC22	Q5TAA0	450
FAM228B	MGARP	Q8TDB4	450
FAM228B	KCTD18	Q6PI47	443
FAM228B	GOLGA6L10	A6NI86	432
FAM228B	STOML2	Q9UJZ1	409
FAM228B	PPP1R42	Q7Z4L9	404
FAM228B	GSKIP	Q9P0R6	403
FAM228B	SPATS2L	Q9NUQ6	403
FAM228B	C2CD2	Q9Y426	398
FAM228B	SERPINA4	P29622	371
FAM228B	C1orf35	Q9BU76	370
FAM228B	VPS35L	Q7Z3J2	359
FAM228B	GTF3A	Q92664	358

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A087WRI3, A2BFC9, A2RRW4, A4QMS7, A6NJV1, A6NL82, A6QPC0, A6QQ68, A8E4X8, A8E5W8, A8QW39, A9JS51, D6REC4, F1P3Y5, G3X6E2, P0C875, Q0VB26, Q1MSJ5, Q2IA00, Q2T9Q3, Q2TA11, Q3UY96, Q494V2, Q497Q6, Q4KKZ1, Q4QR77, Q4R5Y0, Q4R8V8, Q5NC57, Q5ZIH9, Q6J272, Q6PII3, Q6ZQR2, Q6ZVS7, Q7Z4T9, Q8CFW7, Q8N1D5, Q8N6G2, Q8WW14, Q95LR0

Diamond homologs: A6QQ68, P0C875, Q32KQ1, Q497Q6, Q5XIN5, Q8CDW1, Q86W67

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	19
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3931 predictions. Top by Δscore:

Variant	Effect	Δscore
2:24077762:C:CC	acceptor_gain	1.0000
2:24080814:TTTA:T	donor_loss	1.0000
2:24080815:TTAC:T	donor_loss	1.0000
2:24080816:TA:T	donor_loss	1.0000
2:24080817:ACCTT:A	donor_loss	1.0000
2:24080818:C:CA	donor_loss	1.0000
2:24085052:T:TA	donor_gain	1.0000
2:24119575:A:AC	donor_gain	1.0000
2:24119575:AC:A	donor_gain	1.0000
2:24119576:C:CC	donor_gain	1.0000
2:24119576:CC:C	donor_gain	1.0000
2:24119680:CTC:C	acceptor_gain	1.0000
2:24119683:C:CC	acceptor_gain	1.0000
2:24121161:A:AC	donor_gain	1.0000
2:24121162:C:CC	donor_gain	1.0000
2:24122417:A:AC	donor_gain	1.0000
2:24122418:C:CC	donor_gain	1.0000
2:24123213:C:A	donor_gain	1.0000
2:24123636:G:GT	donor_gain	1.0000
2:24167681:G:T	donor_gain	1.0000
2:24077760:TA:T	acceptor_gain	0.9900
2:24081028:TTTC:T	acceptor_gain	0.9900
2:24081029:TTC:T	acceptor_gain	0.9900
2:24081030:TC:T	acceptor_gain	0.9900
2:24081031:CC:C	acceptor_gain	0.9900
2:24081032:C:CC	acceptor_gain	0.9900
2:24081032:C:CG	acceptor_loss	0.9900
2:24081038:C:CT	acceptor_gain	0.9900
2:24081039:A:T	acceptor_gain	0.9900
2:24082999:A:AC	donor_gain	0.9900

AlphaMissense

2155 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:24137978:T:A	W80R	0.989
2:24137978:T:C	W80R	0.989
2:24137980:G:C	W80C	0.982
2:24137980:G:T	W80C	0.982
2:24147034:T:A	W212R	0.969
2:24147034:T:C	W212R	0.969
2:24138077:T:C	F113L	0.962
2:24138079:T:A	F113L	0.962
2:24138079:T:G	F113L	0.962
2:24147064:A:C	S222R	0.960
2:24147066:T:A	S222R	0.960
2:24147066:T:G	S222R	0.960
2:24137979:G:C	W80S	0.947
2:24146930:G:T	G177V	0.943
2:24137993:G:C	A85P	0.942
2:24147036:G:C	W212C	0.939
2:24147036:G:T	W212C	0.939
2:24139379:T:C	F124L	0.936
2:24139381:T:A	F124L	0.936
2:24139381:T:G	F124L	0.936
2:24138078:T:C	F113S	0.932
2:24147070:T:C	F224L	0.921
2:24147072:T:A	F224L	0.921
2:24147072:T:G	F224L	0.921
2:24138003:T:C	L88P	0.918
2:24139415:T:C	F136L	0.912
2:24139417:T:A	F136L	0.912
2:24139417:T:G	F136L	0.912
2:24146771:C:A	D155E	0.910
2:24146771:C:G	D155E	0.910

dbSNP variants (sampled 300 via entrez): RS1000012539 (2:24081068 A>G), RS1000118848 (2:24087158 T>C), RS1000149442 (2:24164450 G>T), RS1000201539 (2:24106398 C>T), RS1000205395 (2:24084410 A>G), RS1000239971 (2:24150522 T>A,G), RS1000245027 (2:24164379 A>C,G), RS1000247269 (2:24112375 A>G), RS1000276486 (2:24106026 A>G), RS1000361893 (2:24150182 A>G), RS1000369495 (2:24080459 C>T), RS1000380587 (2:24112782 T>C), RS1000396426 (2:24156929 G>A,T), RS1000403861 (2:24125930 A>G), RS1000436993 (2:24120208 G>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:190300

GenCC curated gene-disease

Mondo (1): essential tremor (MONDO:0003233)

Orphanet (1): NON RARE IN EUROPE: Hereditary essential tremor (Orphanet:862)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002398_521	Neutrophil count	6.000000e-20

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020329	Essential Tremor	C10.228.662.350

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression, decreases expression	2
Benzo(a)pyrene	affects methylation, increases mutagenesis	2
Nickel	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
perfluorooctanoic acid	increases expression	1
licochalcone B	increases expression	1
Sunitinib	increases expression	1
Quercetin	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00439699	PHASE4	COMPLETED	A Pilot Clinical Trial Of Memantine for Essential Tremor
NCT00584376	PHASE4	COMPLETED	Pregabalin (Lyrica) for the Treatment of Essential Tremor
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02111369	PHASE4	COMPLETED	Propranolol and Botulinum Toxin for Essential Vocal Tremor
NCT02495883	PHASE4	COMPLETED	Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response
NCT00018564	PHASE3	COMPLETED	Novel Therapies for Essential Tremor
NCT00236496	PHASE3	COMPLETED	A Comparison of the Efficacy and Safety of Topiramate Versus Placebo in Treating Tremor of Unknown Cause.
NCT01441284	PHASE3	WITHDRAWN	Efficacy of Pramipexole Extended Release in the Treatment of Essential Tremor
NCT04193527	PHASE3	COMPLETED	A Study to Evaluate the Diagnostic Efficacy of DaTSCAN™ Ioflupane (123I) Injection in Single Photon Emission Computed Tomography (SPECT) for the Diagnosis of Parkinsonian Syndrome (PS) in Chinese Patients
NCT04265209	PHASE3	COMPLETED	[18F] LBT-999 PET Compared to [123I]-FP/CIT SPECT to Distinguish Between Parkinson’s Diseases and Essential Tremor
NCT06087276	PHASE3	ENROLLING_BY_INVITATION	Essential 3 - Decentralized, Phase 3 Study Evaluating the Safety and Efficacy of Ulixacaltamide in Essential Tremor (ET)
NCT00080366	PHASE2	COMPLETED	Octanol to Treat Essential Tremor
NCT00102596	PHASE2	COMPLETED	Clinical Trial Characterizing the Bioavailability of 1-Octanol in Adults With Ethanol-responsive Essential Tremor
NCT00223743	PHASE2	COMPLETED	A Safety/Efficacy Trial of Zonisamide for Essential Tremor
NCT00321087	PHASE2	TERMINATED	A Study of T2000 in Essential Tremor
NCT00598078	PHASE2	COMPLETED	Multiple-dose,Double-blind,Placebo-controlled Study of Sodium Oxybate in Patients With Essential Tremor
NCT00655278	PHASE2	TERMINATED	T2000 in Essential Tremor - Open Label Continuation
NCT01332695	PHASE2	COMPLETED	A Pilot Efficacy and Safety Study of ST101 in Essential Tremor
NCT02277106	PHASE2	COMPLETED	Evaluate SAGE-547 in Participants With Essential Tremor
NCT02551848	PHASE2	UNKNOWN	Kinematic-based BoNT-A Injections for Bilateral ET
NCT02668146	PHASE2	UNKNOWN	An Efficacy/Safety Study of Perampanel for Reducing Essential Tremor
NCT02978781	PHASE2	COMPLETED	A Study to Evaluate SAGE-217 in Participants With Essential Tremor
NCT03101241	PHASE2	COMPLETED	A Phase 2 RCT Study of CX-8998 for Essential Tremor
NCT03688685	PHASE2	COMPLETED	A Clinical Study to Evaluate CAD-1883 in Essential Tremor
NCT03780426	PHASE2	COMPLETED	tSMS in Essential Tremor
NCT04305275	PHASE2	COMPLETED	A Study to Evaluate the Efficacy, Safety, and Tolerability of SAGE-324 in Participants With Essential Tremor
NCT04727658	PHASE2	TERMINATED	Linac FRACtionated Radiosurgical THALamotomie in Tremors (FRACTHAL)
NCT04880616	PHASE2	COMPLETED	Safety, Efficacy, and Tolerability of NBI-827104 for the Treatment of Essential Tremor
NCT05021978	PHASE2	COMPLETED	A Clinical Trial of PRAX-944 in Participants With Essential Tremor
NCT05021991	PHASE2	COMPLETED	A Clinical Trial of 2 Doses of PRAX-944 in Participants With Essential Tremor
NCT05122650	PHASE2	COMPLETED	A Study To Assess the Safety and Efficacy of JZP385 in the Treatment of Adults With Moderate to Severe Essential Tremor (ET)
NCT05173012	PHASE2	COMPLETED	Study to Evaluate SAGE-324 in Participants With Essential Tremor
NCT05387642	PHASE2	WITHDRAWN	A Clinical Trial of PRAX-114 in Participants With Essential Tremor
NCT06312800	PHASE2	WITHDRAWN	Acamprosate and Methazolamide for Essential Tremor
NCT06821906	PHASE2	RECRUITING	Stereotactic Radiosurgery in the Treatment of Essential Tremor
NCT07074002	PHASE2	RECRUITING	Proof of Concept Study on BP1.4979 Effect on Essential Tremor
NCT07103265	PHASE2	NOT_YET_RECRUITING	Developing a New LIFU Neuromodulation Method to Suppress Tremor
NCT00001986	PHASE1	COMPLETED	1-Octanol to Treat Essential Tremor
NCT00016679	PHASE1	COMPLETED	1-Octanol to Treat Essential Tremor
NCT01304758	PHASE1	COMPLETED	ExAblate Transcranial MR Guided Focused Ultrasound in the Treatment of Essential Tremor