FAM89B

Summary

FAM89B (family with sequence similarity 89 member B, HGNC:16708) is a protein-coding gene on chromosome 11q13.1, encoding Leucine repeat adapter protein 25 (Q8N5H3). Negatively regulates TGF-beta-induced signaling; in cooperation with SKI prevents the translocation of SMAD2 from the nucleus to the cytoplasm in response to TGF-beta.

Predicted to enable transcription corepressor binding activity. Predicted to be involved in establishment of cell polarity; negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway; and positive regulation of cell migration. Predicted to be located in cell projection. Predicted to be active in cytoplasm and lamellipodium.

Source: NCBI Gene 23625 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_001098785

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16708
Approved symbol	FAM89B
Name	family with sequence similarity 89 member B
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	MTVR1, LRAP25
Ensembl gene	ENSG00000176973
Ensembl biotype	protein_coding
OMIM	616128
Entrez	23625

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000316409, ENST00000449319, ENST00000530349, ENST00000896147, ENST00000896148

RefSeq mRNA: 3 — MANE Select: NM_001098785 NM_001098784, NM_001098785, NM_152832

CCDS: CCDS44648, CCDS53662, CCDS8105

Canonical transcript exons

ENST00000530349 — 2 exons

Exon	Start	End
ENSE00002176121	65572538	65572960
ENSE00002181083	65573363	65574190

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.1893 / max 123.5315, expressed in 1806 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115173	22.6465	1806
115174	0.5428	337

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.00	gold quality
gastrocnemius	UBERON:0001388	95.88	gold quality
right coronary artery	UBERON:0001625	95.63	gold quality
granulocyte	CL:0000094	95.50	gold quality
ganglionic eminence	UBERON:0004023	95.27	gold quality
muscle of leg	UBERON:0001383	95.23	gold quality
leukocyte	CL:0000738	94.74	gold quality
monocyte	CL:0000576	94.71	gold quality
apex of heart	UBERON:0002098	94.63	gold quality
thoracic aorta	UBERON:0001515	94.62	gold quality
ascending aorta	UBERON:0001496	94.60	gold quality
left coronary artery	UBERON:0001626	94.37	gold quality
descending thoracic aorta	UBERON:0002345	94.29	gold quality
right frontal lobe	UBERON:0002810	93.93	gold quality
lower esophagus mucosa	UBERON:0035834	93.93	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.86	gold quality
blood	UBERON:0000178	93.80	gold quality
primary visual cortex	UBERON:0002436	93.73	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.73	gold quality
lower esophagus	UBERON:0013473	93.72	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.72	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.63	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.62	gold quality
anterior cingulate cortex	UBERON:0009835	93.53	gold quality
popliteal artery	UBERON:0002250	93.52	gold quality
tibial artery	UBERON:0007610	93.50	gold quality
amygdala	UBERON:0001876	93.47	gold quality
temporal lobe	UBERON:0001871	93.46	gold quality
Ammon’s horn	UBERON:0001954	93.44	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	6.63
E-ANND-3	yes	5.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting FAM89B, 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-12119	99.87	68.35	1653
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-5011-3P	98.63	64.81	638
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-6751-3P	98.44	66.35	835
HSA-MIR-1199-5P	98.44	66.51	829
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-5586-5P	96.29	68.02	685
HSA-MIR-1293	96.16	64.69	916
HSA-MIR-4524B-3P	95.52	64.12	964
HSA-MIR-6823-3P	95.45	66.14	704

Literature-anchored findings (GeneRIF, showing 2)

• identified two human genes, Mtvr1 and Mtvr2, encoding proteins highly related to the Mouse Mammary Tumor Virus receptor [Mtvr1] [Mtvr2] (PMID:11958456)
• the functional relevance of the LRAP25-MRCK complex in LIMK1-cofilin signaling and the importance of LRAP adaptors as key determinants of MRCK cellular localization and downstream specificities. (PMID:25107909)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam89b	ENSDARG00000069106
mus_musculus	Fam89b	ENSMUSG00000024939
rattus_norvegicus	Fam89b	ENSRNOG00000024239
drosophila_melanogaster	CG31038	FBGN0051038
drosophila_melanogaster	lmgB	FBGN0085470

Paralogs (2): TRANK1 (ENSG00000168016), FAM89A (ENSG00000182118)

Protein

Protein identifiers

Leucine repeat adapter protein 25 — Q8N5H3 (reviewed: Q8N5H3)

All UniProt accessions (1): Q8N5H3

UniProt curated annotations — full annotation on UniProt →

Function. Negatively regulates TGF-beta-induced signaling; in cooperation with SKI prevents the translocation of SMAD2 from the nucleus to the cytoplasm in response to TGF-beta. Acts as an adapter that mediates the specific recognition of LIMK1 by CDC42BPA and CDC42BPB in the lamellipodia. LRAP25-mediated CDC42BPA/CDC42BPB targeting to LIMK1 and the lamellipodium results in LIMK1 activation and the subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation.

Subunit / interactions. Interacts with SKI. Interacts (via LRR repeat) with CDC42BPA (via AGC-kinase C-terminal domain), CDC42BPB (via AGC-kinase C-terminal domain) and LIMK1 (via LIM zinc-binding domains). Forms a tripartite complex with CDC42BPA, CDC42BPB and LIMK1.

Subcellular location. Cytoplasm. Cell projection. Lamellipodium.

Similarity. Belongs to the FAM89 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8N5H3-3	3	yes
Q8N5H3-1	1
Q8N5H3-2	2
Q8N5H3-4	4

RefSeq proteins (3): NP_001092254, NP_001092255, NP_690045 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR039499	LURA1/LRA25	Family

Pfam: PF14854

UniProt features (12 total): splice variant 4, region of interest 2, compositionally biased region 2, modified residue 2, chain 1, repeat 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N5H3-F1	70.13	0.23

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 (2): 28, 188

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 168 (showing top): GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, AP2_Q3, GGGTGGRR_PAX4_03, chr11q13, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, GROSS_HYPOXIA_VIA_ELK3_UP, WTGAAAT_UNKNOWN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA_STIMULUS, PEART_HDAC_PROLIFERATION_CLUSTER_UP, GOBP_RESPONSE_TO_GROWTH_FACTOR

GO Biological Process (4): establishment of cell polarity (GO:0030010), positive regulation of cell migration (GO:0030335), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), negative regulation of SMAD protein signal transduction (GO:0060392)

GO Molecular Function (1): transcription corepressor binding (GO:0001222)

GO Cellular Component (3): cytoplasm (GO:0005737), lamellipodium (GO:0030027), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	2
cellular anatomical structure	2
establishment or maintenance of cell polarity	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
regulation of SMAD protein signal transduction	1
SMAD protein signal transduction	1
negative regulation of intracellular signal transduction	1
transcription coregulator binding	1
intracellular anatomical structure	1
cell leading edge	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

833 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM89B	SLC25A45	Q8N413	614
FAM89B	ZNRD2	O60232	591
FAM89B	SLC66A2	Q8N2U9	576
FAM89B	RIIAD1	A6NNX1	562
FAM89B	TM7SF3	Q9NS93	549
FAM89B	TIGD3	Q6B0B8	545
FAM89B	FRMD8	Q9BZ67	541
FAM89B	PRPF38B	Q5VTL8	519
FAM89B	SCOC	Q9UIL1	506
FAM89B	KCNK7	Q9Y2U2	503
FAM89B	CDC42EP2	O14613	492
FAM89B	URB2	Q14146	478
FAM89B	MAP3K11	Q16584	478
FAM89B	DLGAP3	O95886	470
FAM89B	LTBP3	Q9NS15	469

IntAct

9 interactions, top by confidence:

A	B	Type	Score
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
FAM89B	PSMG1	psi-mi:“MI:0914”(association)	0.350
DCTN3	RPS6KA4	psi-mi:“MI:0914”(association)	0.350
FAM89B	PSMG2	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): FAM89B (Affinity Capture-RNA), PSMG2 (Affinity Capture-MS), POMP (Affinity Capture-MS), PSMG1 (Affinity Capture-MS), HOOK2 (Affinity Capture-MS), FAM89B (Affinity Capture-MS)

ESM2 similar proteins: A1L168, A1L3T7, A6NGS2, A6QQF7, D4A8G3, O15049, P0C7N2, P0C7N4, P17257, P58660, Q08AY9, Q0V7M8, Q0VDN7, Q14BJ1, Q2NL23, Q3KP66, Q3LUD3, Q3UNU4, Q4LEZ3, Q566R4, Q571B6, Q5BJW5, Q5ND29, Q5RFZ7, Q5XIS1, Q6NSJ2, Q6P1G6, Q6Q0N2, Q7TN12, Q7TSI1, Q811W1, Q8BL43, Q8C7U1, Q8IV03, Q8K1S6, Q8K2P1, Q8N137, Q8N5H3, Q8TE77, Q8WWL2

Diamond homologs: A6QQF7, Q08AY9, Q14BJ1, Q566R4, Q6Q0N2, Q8N5H3, Q96GI7, Q9QUI1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

227 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65572957:GATG:G	donor_gain	1.0000
11:65572961:G:GG	donor_gain	1.0000
11:65572961:GTGA:G	donor_loss	1.0000
11:65572962:T:G	donor_loss	1.0000
11:65572959:TG:T	donor_gain	0.9900
11:65572960:GG:G	donor_gain	0.9900
11:65572956:AGATG:A	donor_gain	0.9800
11:65572957:GATGG:G	donor_gain	0.9800
11:65572964:A:AG	donor_gain	0.9800
11:65572965:G:GG	donor_gain	0.9800
11:65573351:AGTT:A	acceptor_gain	0.9800
11:65573352:GTTG:G	acceptor_gain	0.9800
11:65573352:GTT:G	acceptor_gain	0.9700
11:65572955:G:GT	donor_gain	0.9600
11:65572958:ATG:A	donor_gain	0.9600
11:65572964:AGTG:A	donor_gain	0.9600
11:65573351:A:AG	acceptor_gain	0.9400
11:65573352:G:GG	acceptor_gain	0.9400
11:65573352:GTTGT:G	acceptor_gain	0.9300
11:65573360:CAGGT:C	acceptor_loss	0.9300
11:65573352:GT:G	acceptor_gain	0.9200
11:65572965:G:C	donor_gain	0.9100
11:65573347:CCTCA:C	acceptor_loss	0.8900
11:65573348:CTCA:C	acceptor_loss	0.8900
11:65573349:TCAGT:T	acceptor_loss	0.8900
11:65573350:CA:C	acceptor_loss	0.8900
11:65573352:G:T	acceptor_loss	0.8900
11:65573401:GCT:G	acceptor_gain	0.8900
11:65572956:A:T	donor_gain	0.8800
11:65572959:TGG:T	donor_gain	0.8800

AlphaMissense

1210 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65572947:T:C	L93P	1.000
11:65572959:T:G	M97R	1.000
11:65573370:T:C	L100P	1.000
11:65573382:A:C	D104A	1.000
11:65573382:A:T	D104V	1.000
11:65573391:T:C	L107S	1.000
11:65573391:T:G	L107W	1.000
11:65573403:T:C	L111P	1.000
11:65573412:T:C	L114P	1.000
11:65573420:T:C	S117P	1.000
11:65572821:T:C	I51T	0.999
11:65572947:T:A	L93Q	0.999
11:65572949:C:A	R94S	0.999
11:65572959:T:A	M97K	0.999
11:65572959:T:C	M97T	0.999
11:65573370:T:A	L100Q	0.999
11:65573381:G:A	D104N	0.999
11:65573381:G:C	D104H	0.999
11:65573381:G:T	D104Y	0.999
11:65573382:A:G	D104G	0.999
11:65573383:C:A	D104E	0.999
11:65573383:C:G	D104E	0.999
11:65573387:T:C	S106P	0.999
11:65573394:T:C	L108S	0.999
11:65573424:T:A	I118N	0.999
11:65573437:A:C	K122N	0.999
11:65573437:A:T	K122N	0.999
11:65572749:T:A	L27H	0.998
11:65572938:T:C	L90P	0.998
11:65572950:G:C	R94P	0.998

dbSNP variants (sampled 300 via entrez): RS1000708681 (11:65573300 GGGGGC>G,GGGGGCGGGGC), RS1001877977 (11:65573746 C>G), RS1001940599 (11:65574159 G>A), RS1003738204 (11:65572311 G>C), RS1005296280 (11:65571205 C>T), RS1006188049 (11:65572510 G>A), RS1006300889 (11:65572755 G>A,T), RS1007775895 (11:65571372 C>T), RS1007954592 (11:65573284 G>A,C,T), RS1008394991 (11:65574355 G>A), RS1008447055 (11:65574531 C>A,T), RS1008764388 (11:65573106 C>A,T), RS1008775747 (11:65573531 G>A), RS1009354947 (11:65573384 A>G), RS1011237933 (11:65573829 C>T)

Disease associations

OMIM: gene MIM:616128 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002481_8	Acne (severe)	3.000000e-11
GCST005194_195	Coronary artery disease	3.000000e-10

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
Valproic Acid	increases expression	3
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
trichostatin A	affects expression	1
cupric chloride	increases expression	1
tamibarotene	increases expression	1
licochalcone B	increases expression	1
(+)-JQ1 compound	increases expression	1
MT19c compound	decreases expression	1
Temozolomide	decreases expression	1
Cadmium	increases expression	1
Methotrexate	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Vitamin E	increases expression	1
Aflatoxin B1	increases expression	1
Palmitic Acid	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1
Acrylamide	decreases expression	1
Vitamin K 3	affects expression	1

Clinical trials (associated diseases)

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