FAM168B

Summary

FAM168B (family with sequence similarity 168 member B, HGNC:27016) is a protein-coding gene on chromosome 2q21.1, encoding Myelin-associated neurite-outgrowth inhibitor (A1KXE4). Inhibitor of neuronal axonal outgrowth.

Predicted to act upstream of or within axonogenesis and gene expression. Located in extracellular exosome.

Source: NCBI Gene 130074 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_001009993

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27016
Approved symbol	FAM168B
Name	family with sequence similarity 168 member B
Location	2q21.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0280L, MANI
Ensembl gene	ENSG00000152102
Ensembl biotype	protein_coding
OMIM	620078
Entrez	130074

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 35 protein_coding

ENST00000389915, ENST00000409185, ENST00000894388, ENST00000894389, ENST00000894390, ENST00000894391, ENST00000894392, ENST00000894393, ENST00000894394, ENST00000894395, ENST00000894396, ENST00000894397, ENST00000894398, ENST00000894399, ENST00000894400, ENST00000894401, ENST00000894402, ENST00000894403, ENST00000894404, ENST00000894405, ENST00000894406, ENST00000894407, ENST00000894408, ENST00000894409, ENST00000894410, ENST00000894411, ENST00000894412, ENST00000894413, ENST00000930096, ENST00000930097, ENST00000954277, ENST00000954279, ENST00000954281, ENST00000954283, ENST00000954285

RefSeq mRNA: 7 — MANE Select: NM_001009993 NM_001009993, NM_001321743, NM_001321744, NM_001321745, NM_001321746, NM_001321747, NM_001321748

CCDS: CCDS42755

Canonical transcript exons

ENST00000389915 — 7 exons

Exon	Start	End
ENSE00001377041	131071855	131071938
ENSE00001427654	131093214	131093460
ENSE00001433693	131082577	131082657
ENSE00001507257	131052891	131053015
ENSE00001507258	131055272	131055449
ENSE00001507259	131055553	131055695
ENSE00001579690	131047876	131052452

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.3785 / max 325.6449, expressed in 1820 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30632	45.6248	1818
30631	1.7917	951
30626	0.6939	380
30629	0.1865	53
30630	0.0815	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral globus pallidus	UBERON:0002476	98.10	gold quality
cerebellar vermis	UBERON:0004720	97.99	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.98	gold quality
pons	UBERON:0000988	97.68	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.55	gold quality
middle frontal gyrus	UBERON:0002702	97.54	gold quality
parietal lobe	UBERON:0001872	97.40	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.38	gold quality
postcentral gyrus	UBERON:0002581	97.37	gold quality
superior vestibular nucleus	UBERON:0007227	97.28	gold quality
medulla oblongata	UBERON:0001896	97.11	gold quality
frontal pole	UBERON:0002795	97.11	gold quality
orbitofrontal cortex	UBERON:0004167	97.07	gold quality
subthalamic nucleus	UBERON:0001906	97.05	gold quality
inferior vagus X ganglion	UBERON:0005363	97.02	gold quality
secondary oocyte	CL:0000655	96.94	gold quality
substantia nigra pars compacta	UBERON:0001965	96.93	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.79	gold quality
cortical plate	UBERON:0005343	96.70	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.67	gold quality
middle temporal gyrus	UBERON:0002771	96.64	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.57	gold quality
ventricular zone	UBERON:0003053	96.47	gold quality
superior frontal gyrus	UBERON:0002661	96.44	gold quality
prefrontal cortex	UBERON:0000451	96.29	gold quality
putamen	UBERON:0001874	96.28	gold quality
paraflocculus	UBERON:0005351	96.27	gold quality
olfactory bulb	UBERON:0002264	96.24	silver quality
ganglionic eminence	UBERON:0004023	96.23	gold quality
globus pallidus	UBERON:0001875	96.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

234 targeting FAM168B, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-557	99.96	70.01	1640

Literature-anchored findings (GeneRIF, showing 1)

• novel protein MANI (myelin-associated neurite-outgrowth inhibitor)localizes to neural membranes; findings describe the novel MANI-Cdc27-APC pathway as an important cascade that prevents neurons from extending axons (PMID:20716133)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam168b	ENSDARG00000101733
mus_musculus	Fam168b	ENSMUSG00000037503
rattus_norvegicus	Fam168b	ENSRNOG00000023467

Paralogs (1): FAM168A (ENSG00000054965)

Protein

Protein identifiers

Myelin-associated neurite-outgrowth inhibitor — A1KXE4 (reviewed: A1KXE4)

Alternative names: p20

All UniProt accessions (1): A1KXE4

UniProt curated annotations — full annotation on UniProt →

Function. Inhibitor of neuronal axonal outgrowth. Acts as a negative regulator of CDC42 and STAT3 and a positive regulator of STMN2. Positive regulator of CDC27.

Subunit / interactions. May form homodimers. May interact with DAZAP2, FAM168A, PRDX6, RBM6, TMTC1 and YPEL2. Interacts with CDC27.

Subcellular location. Cytoplasm. Perinuclear region. Cell membrane. Cell projection. Axon.

Tissue specificity. Expressed in the brain, within neuronal axonal fibers and associated with myelin sheets (at protein level). Expression tends to be lower in the brain of Alzheimer disease patients compared to healthy individuals (at protein level).

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the FAM168 family.

Isoforms (2)

UniProt ID	Names	Canonical?
A1KXE4-1	1	yes
A1KXE4-2	2

RefSeq proteins (7): NP_001009993, NP_001308672, NP_001308673, NP_001308674, NP_001308675, NP_001308676, NP_001308677 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029247	FAM168A/MANI	Family

Pfam: PF14944

UniProt features (11 total): topological domain 3, transmembrane region 2, modified residue 2, chain 1, sequence conflict 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A1KXE4-F1	50.01	0.00

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): 1, 6

Glycosylation sites (1): 46

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 207 (showing top): GCM_MAP4K4, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GCM_GSPT1, MORF_SNRP70, MORF_UBE2I, MORF_HDAC1, GTTAAAG_MIR302B, MITSIADES_RESPONSE_TO_APLIDIN_DN, ACTGCAG_MIR173P, BROWNE_HCMV_INFECTION_48HR_DN, MORF_RAF1, MORF_CCNI, MORF_CTBP1, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (7): plasma membrane (GO:0005886), axon (GO:0030424), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
membrane	1
cell periphery	1
neuron projection	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM168B	RTN4R	Q9BZR6	677
FAM168B	WSB2	Q9NYS7	463
FAM168B	CMTM4	Q8IZR5	459
FAM168B	GAGE12H	A6NDE8	445
FAM168B	AMER3	Q8N944	430
FAM168B	CD180	Q99467	414
FAM168B	GPR148	Q8TDV2	406
FAM168B	LYSMD1	Q96S90	394
FAM168B	SEL1L2	Q5TEA6	394
FAM168B	RTN4	Q9NQC3	389
FAM168B	GAGE12B	A1L429	380
FAM168B	RGMA	Q96B86	374
FAM168B	RBM48	Q5RL73	371
FAM168B	PLEKHB2	Q96CS7	370
FAM168B	PTPN14	Q15678	359

IntAct

8 interactions, top by confidence:

A	B	Type	Score
PARP2	FAM168B	psi-mi:“MI:0557”(adp ribosylation reaction)	0.440
gB	FAM168B	psi-mi:“MI:0915”(physical association)	0.370
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
KSR1	FAM168B	psi-mi:“MI:0914”(association)	0.350
KSR1		psi-mi:“MI:0914”(association)	0.350
IFIH1	FAM168B	psi-mi:“MI:0914”(association)	0.350
ENG	IGKV2-28	psi-mi:“MI:0914”(association)	0.350

BioGRID (58): FAM168B (Affinity Capture-RNA), FAM168B (Affinity Capture-MS), FAM168B (Two-hybrid), FAM168B (Two-hybrid), FAM168B (Two-hybrid), FAM168B (Two-hybrid), FAM168B (Two-hybrid), FAM168B (Two-hybrid), FAM168B (Two-hybrid), FAM168B (Two-hybrid), FAM168B (Two-hybrid), FAM168B (Two-hybrid), FAM168B (Two-hybrid), FAM168B (Two-hybrid), FAM168B (Two-hybrid)

ESM2 similar proteins: A0JNC2, A1KXE4, A8E639, A8MV65, D4AEP3, E3X5D6, P05411, P12981, P18870, P54864, P60486, Q08BY2, Q0IHC4, Q0VFP2, Q14157, Q15032, Q15038, Q157S1, Q16656, Q3LRZ1, Q3T0A9, Q3T0K9, Q3U182, Q4R5H7, Q53ET0, Q58D45, Q5BJ83, Q5R526, Q5RDV6, Q5U2U6, Q5XIH2, Q5ZIS9, Q68ED7, Q6PEH8, Q7PXU6, Q80TM6, Q80X50, Q80XQ8, Q8AVW3, Q8BGZ2

Diamond homologs: A1KXE4, A8E639, D4AEP3, Q08BY2, Q0IHC4, Q0VFP2, Q80XQ8, Q8BGZ2, Q92567

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1871 predictions. Top by Δscore:

Variant	Effect	Δscore
2:131052375:T:TA	donor_gain	1.0000
2:131052885:ACTT:A	donor_loss	1.0000
2:131052887:TTACA:T	donor_loss	1.0000
2:131052888:TAC:T	donor_loss	1.0000
2:131052889:A:AC	donor_gain	1.0000
2:131052890:C:CC	donor_gain	1.0000
2:131052890:CA:C	donor_gain	1.0000
2:131052890:CAT:C	donor_gain	1.0000
2:131052924:G:C	donor_gain	1.0000
2:131053016:C:CA	acceptor_loss	1.0000
2:131055270:A:AC	donor_gain	1.0000
2:131055270:AC:A	donor_gain	1.0000
2:131055271:C:CC	donor_gain	1.0000
2:131055271:CC:C	donor_gain	1.0000
2:131055271:CCTG:C	donor_gain	1.0000
2:131055446:CTTG:C	acceptor_gain	1.0000
2:131055447:TTG:T	acceptor_gain	1.0000
2:131055448:TG:T	acceptor_gain	1.0000
2:131055450:C:CC	acceptor_gain	1.0000
2:131055452:G:C	acceptor_gain	1.0000
2:131055549:ATACC:A	donor_loss	1.0000
2:131071850:CATA:C	donor_loss	1.0000
2:131071851:ATAC:A	donor_loss	1.0000
2:131071854:C:A	donor_loss	1.0000
2:131071935:CCAG:C	acceptor_gain	1.0000
2:131071936:CAG:C	acceptor_gain	1.0000
2:131071936:CAGC:C	acceptor_gain	1.0000
2:131082572:CTTA:C	donor_gain	1.0000
2:131082575:A:AC	donor_gain	1.0000
2:131082576:C:CC	donor_gain	1.0000

AlphaMissense

1227 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:131055400:A:C	I116S	0.997
2:131055400:A:G	I116T	0.997
2:131055400:A:T	I116N	0.997
2:131055391:G:A	T119I	0.995
2:131055398:G:C	H117D	0.995
2:131055395:G:C	H118D	0.994
2:131055296:C:A	G151W	0.992
2:131055280:A:T	M156K	0.991
2:131055403:A:T	V115D	0.991
2:131052908:A:G	W195R	0.990
2:131052908:A:T	W195R	0.990
2:131055388:G:T	T120K	0.989
2:131055394:T:C	H118R	0.989
2:131055286:A:T	M154K	0.988
2:131055280:A:C	M156R	0.987
2:131055283:G:T	A155D	0.987
2:131055289:G:A	T153I	0.987
2:131055308:C:G	G147R	0.987
2:131055388:G:C	T120R	0.987
2:131055272:C:G	G159R	0.985
2:131055382:A:T	V122E	0.985
2:131055286:A:C	M154R	0.984
2:131055385:A:T	V121E	0.984
2:131082594:T:A	K18I	0.984
2:131055393:G:C	H118Q	0.982
2:131055393:G:T	H118Q	0.982
2:131055394:T:A	H118L	0.982
2:131055671:T:A	K60I	0.982
2:131055296:C:G	G151R	0.981
2:131055296:C:T	G151R	0.981

dbSNP variants (sampled 300 via entrez): RS1000002358 (2:131085338 C>T), RS1000016346 (2:131088470 T>A,C), RS1000017595 (2:131072118 T>A,C), RS1000033051 (2:131047838 A>G), RS1000086550 (2:131087375 C>G,T), RS1000100404 (2:131053694 T>C), RS1000145832 (2:131083669 GAAT>G), RS1000177300 (2:131083907 T>TA), RS1000298670 (2:131069166 A>T), RS1000311873 (2:131077948 C>A,T), RS1000327580 (2:131074894 C>T), RS1000424403 (2:131072969 G>C), RS1000430131 (2:131048077 C>G,T), RS1000442157 (2:131074631 T>C), RS1000479071 (2:131084537 T>C)

Disease associations

OMIM: gene MIM:620078 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Arsenic	decreases methylation	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	increases expression	1
Smoke	decreases expression	1
Thimerosal	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis