FAM135A

Summary

FAM135A (family with sequence similarity 135 member A, HGNC:21084) is a protein-coding gene on chromosome 6q13, encoding Protein FAM135A (Q9P2D6).

Predicted to be involved in lipid metabolic process.

Source: NCBI Gene 57579 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 193 total
• MANE Select transcript: NM_001162529

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21084
Approved symbol	FAM135A
Name	family with sequence similarity 135 member A
Location	6q13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20176
Ensembl gene	ENSG00000082269
Ensembl biotype	protein_coding
Entrez	57579

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 32 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000194672, ENST00000361499, ENST00000370479, ENST00000393299, ENST00000418814, ENST00000425415, ENST00000457062, ENST00000505675, ENST00000505769, ENST00000505868, ENST00000507049, ENST00000507085, ENST00000508844, ENST00000514185, ENST00000515280, ENST00000515323, ENST00000856122, ENST00000856123, ENST00000856124, ENST00000856125, ENST00000935394, ENST00000935395, ENST00000935396, ENST00000935397, ENST00000935398, ENST00000935399, ENST00000935400, ENST00000935401, ENST00000935402, ENST00000935403, ENST00000935404, ENST00000935405, ENST00000935406, ENST00000935407, ENST00000954037, ENST00000954038, ENST00000954039, ENST00000954040, ENST00000954041

RefSeq mRNA: 21 — MANE Select: NM_001162529 NM_001105531, NM_001162529, NM_001330995, NM_001330996, NM_001330997, NM_001330998, NM_001330999, NM_001331000, NM_001331001, NM_001331002, NM_001331003, NM_001331004, NM_001331005, NM_001331006, NM_001351599, NM_001351600, NM_001351602, NM_001351607, NM_001351608, NM_001351609, NM_020819

CCDS: CCDS34481, CCDS47448, CCDS55028, CCDS83104

Canonical transcript exons

ENST00000418814 — 22 exons

Exon	Start	End
ENSE00000758461	70524343	70526698
ENSE00001452824	70426439	70426532
ENSE00001452851	70415291	70415376
ENSE00001709616	70428304	70428419
ENSE00002033931	70559716	70561174
ENSE00002046332	70413508	70413702
ENSE00003492761	70536260	70536411
ENSE00003501680	70533160	70533251
ENSE00003501816	70482001	70482154
ENSE00003517825	70538291	70538401
ENSE00003582469	70522513	70522586
ENSE00003582911	70480901	70481027
ENSE00003593568	70502636	70502791
ENSE00003596154	70475410	70475549
ENSE00003600507	70533757	70533854
ENSE00003621259	70477159	70477332
ENSE00003656498	70475663	70475733
ENSE00003674629	70528292	70528452
ENSE00003675941	70452492	70452571
ENSE00003677623	70491034	70491083
ENSE00003684850	70556750	70556863
ENSE00003686169	70523967	70524121

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 98.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.0032 / max 371.2650, expressed in 1629 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68469	15.2418	1614
68468	0.7614	381

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	98.44	gold quality
gingival epithelium	UBERON:0001949	97.58	gold quality
gingiva	UBERON:0001828	96.64	gold quality
lower esophagus mucosa	UBERON:0035834	96.31	gold quality
oral cavity	UBERON:0000167	95.72	gold quality
jejunal mucosa	UBERON:0000399	95.21	gold quality
upper leg skin	UBERON:0004262	95.06	gold quality
tibia	UBERON:0000979	94.64	gold quality
esophagus mucosa	UBERON:0002469	93.95	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.12	gold quality
colonic mucosa	UBERON:0000317	92.98	gold quality
palpebral conjunctiva	UBERON:0001812	92.48	gold quality
germinal epithelium of ovary	UBERON:0001304	92.43	gold quality
skin of hip	UBERON:0001554	92.14	gold quality
calcaneal tendon	UBERON:0003701	91.69	gold quality
secondary oocyte	CL:0000655	91.21	gold quality
eye	UBERON:0000970	90.37	gold quality
epithelium of esophagus	UBERON:0001976	90.31	gold quality
amniotic fluid	UBERON:0000173	90.27	gold quality
rectum	UBERON:0001052	90.09	gold quality
skin of abdomen	UBERON:0001416	89.50	gold quality
duodenum	UBERON:0002114	89.42	gold quality
mucosa of transverse colon	UBERON:0004991	89.26	gold quality
skin of leg	UBERON:0001511	89.18	gold quality
cerebellar vermis	UBERON:0004720	88.99	gold quality
vagina	UBERON:0000996	88.97	gold quality
epithelium of nasopharynx	UBERON:0001951	88.79	gold quality
pharyngeal mucosa	UBERON:0000355	88.71	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.67	gold quality
cortical plate	UBERON:0005343	88.60	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.29
E-GEOD-137537	yes	5.26
E-GEOD-100618	no	402.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

151 targeting FAM135A, 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-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642

Literature-anchored findings (GeneRIF, showing 1)

• LncRNA MIR17HG Suppresses Breast Cancer Proliferation and Migration as ceRNA to Target FAM135A by Sponging miR-454-3p. (PMID:36943627)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam135a	ENSDARG00000059843
mus_musculus	Fam135a	ENSMUSG00000026153
rattus_norvegicus	Fam135a	ENSRNOG00000013587
drosophila_melanogaster	CG32333	FBGN0052333
caenorhabditis_elegans	C09D4.4	WBGENE00015635

Paralogs (1): FAM135B (ENSG00000147724)

Protein

Protein identifiers

Protein FAM135A — Q9P2D6 (reviewed: Q9P2D6)

All UniProt accessions (6): Q9P2D6, D6RC17, D6RCC7, D6REA8, D6RFG9, H7BXC5

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Ubiquitous.

Similarity. Belongs to the FAM135 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9P2D6-1	1	yes
Q9P2D6-2	2
Q9P2D6-3	3
Q9P2D6-4	4

RefSeq proteins (21): NP_001099001, NP_001156001, NP_001317924, NP_001317925, NP_001317926, NP_001317927, NP_001317928, NP_001317929, NP_001317930, NP_001317931, NP_001317932, NP_001317933, NP_001317934, NP_001317935, NP_001338528, NP_001338529, NP_001338531, NP_001338536, NP_001338537, NP_001338538, NP_065870 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007751	DUF676_lipase-like	Domain
IPR022122	DUF3657	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR044294	Lipase-like	Family

Pfam: PF05057, PF12394

UniProt features (14 total): splice variant 4, sequence variant 3, region of interest 2, sequence conflict 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2D6-F1	60.24	0.31

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9696273	RND1 GTPase cycle

MSigDB gene sets: 192 (showing top): TATTATA_MIR374, CHANDRAN_METASTASIS_DN, COATES_MACROPHAGE_M1_VS_M2_UP, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_LIPID_METABOLIC_PROCESS, DOUGLAS_BMI1_TARGETS_UP, TAATGTG_MIR323, CUI_TCF21_TARGETS_2_DN, AACTGGA_MIR145, AGCATTA_MIR155, XU_GH1_EXOGENOUS_TARGETS_DN, MARSON_BOUND_BY_FOXP3_STIMULATED, GTATTAT_MIR3693P, REACTOME_RHO_GTPASE_CYCLE, TAVAZOIE_METASTASIS

GO Biological Process (1): lipid metabolic process (GO:0006629)

GO Molecular Function (0):

GO Cellular Component (0):

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1

Protein interactions and networks

STRING

436 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM135A	A0A3B3ISG8	A0A3B3ISG8	570
FAM135A	FAM81A	Q8TBF8	442
FAM135A	ZNF727	A8MUV8	434
FAM135A	CHAC2	Q8WUX2	397
FAM135A	ABHD10	Q9NUJ1	396
FAM135A	ABHD13	Q7L211	395
FAM135A	ABHD14A	Q9BUJ0	387
FAM135A	ABHD16B	Q9H3Z7	386
FAM135A	TMED6	Q8WW62	385
FAM135A	TEX30	Q5JUR7	375
FAM135A	C11orf65	Q8NCR3	375
FAM135A	PRR32	B1ATL7	374
FAM135A	MTRNR2L10	P0CJ77	373
FAM135A	CCDC148	Q8NFR7	371
FAM135A	ZNF726	A6NNF4	370

IntAct

37 interactions, top by confidence:

A	B	Type	Score
EEA1	IGF2R	psi-mi:“MI:2364”(proximity)	0.450
FAM135A		psi-mi:“MI:0915”(physical association)	0.370
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
rep	VWA8	psi-mi:“MI:0914”(association)	0.350
CLNS1A	EPB41	psi-mi:“MI:0914”(association)	0.350
GLUL	SUB1	psi-mi:“MI:0914”(association)	0.350
RPL11	RPS3A	psi-mi:“MI:0914”(association)	0.350
TUBA1B	SLAIN2	psi-mi:“MI:0914”(association)	0.350
UBA52	VCP	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
BET1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
EEA1	PPIP5K2	psi-mi:“MI:2364”(proximity)	0.270
EEA1	PDLIM1	psi-mi:“MI:2364”(proximity)	0.270
EZR	EEF2K	psi-mi:“MI:2364”(proximity)	0.270
LAMP1	TRAPPC13	psi-mi:“MI:2364”(proximity)	0.270
RAB5A	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
RAB9A	SNAP23	psi-mi:“MI:2364”(proximity)	0.270
TGOLN2	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
TGOLN2	TRAPPC13	psi-mi:“MI:2364”(proximity)	0.270
sifA	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
EGFR	FAM171A2	psi-mi:“MI:2364”(proximity)	0.270
EPHA4	FAM171A2	psi-mi:“MI:2364”(proximity)	0.270
EPHA5	C1orf226	psi-mi:“MI:2364”(proximity)	0.270
EPHA7	PIK3R2	psi-mi:“MI:2364”(proximity)	0.270
EPHA8	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
FGFR1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
FGFR2	APBB1	psi-mi:“MI:2364”(proximity)	0.270
FGFR4	SH3PXD2B	psi-mi:“MI:2364”(proximity)	0.270
AATK	CNOT1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (104): FAM135A (Affinity Capture-MS), FAM135A (Affinity Capture-MS), FAM135A (Affinity Capture-RNA), FAM135A (Proximity Label-MS), FAM135A (Proximity Label-MS), FAM135A (Proximity Label-MS), FAM135A (Proximity Label-MS), FAM135A (Proximity Label-MS), FAM135A (Proximity Label-MS), FAM135A (Proximity Label-MS), FAM135A (Proximity Label-MS), FAM135A (Proximity Label-MS), FAM135A (Affinity Capture-RNA), FAM135A (Proximity Label-MS), FAM135A (Proximity Label-MS)

ESM2 similar proteins: A0A087WXM9, A0A2K1JJ00, A0JM83, A4IGL8, E1BC15, E9Q5F9, O14513, O35923, O60673, O88491, P46013, P97929, Q14B71, Q28DZ0, Q29RT4, Q3MHH3, Q3TNU4, Q3ZBP0, Q4QY64, Q4V7J0, Q5DTT3, Q5E9A0, Q5F2C3, Q5RD08, Q5VWN6, Q5VYV7, Q61493, Q69YH5, Q6NS59, Q703I1, Q80U59, Q86XD8, Q8IXS0, Q8IYL3, Q8L7I1, Q8N7Z5, Q8NFU7, Q8TEP8, Q92628, Q96BU1

Diamond homologs: Q49AJ0, Q5RA75, Q641I1, Q6NS59, Q9DAI6, Q9P2D6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Constitutive Signaling by Aberrant PI3K in Cancer	7	22.2×	1e-05
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	7	16.9×	4e-05
PIP3 activates AKT signaling	7	11.7×	3e-04
Clathrin-mediated endocytosis	5	10.7×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein autophosphorylation	5	15.4×	3e-03
positive regulation of MAPK cascade	6	10.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	165
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4691 predictions. Top by Δscore:

Variant	Effect	Δscore
6:70426478:G:GT	donor_gain	1.0000
6:70428300:A:AG	acceptor_gain	1.0000
6:70428416:GAGG:G	donor_gain	1.0000
6:70428418:GG:G	donor_gain	1.0000
6:70428419:GG:G	donor_gain	1.0000
6:70428420:G:GG	donor_gain	1.0000
6:70428420:GT:G	donor_loss	1.0000
6:70428421:TAT:T	donor_loss	1.0000
6:70452490:A:AG	acceptor_gain	1.0000
6:70452491:G:GA	acceptor_gain	1.0000
6:70452491:GT:G	acceptor_gain	1.0000
6:70452491:GTT:G	acceptor_gain	1.0000
6:70452491:GTTT:G	acceptor_gain	1.0000
6:70452567:AACAG:A	donor_loss	1.0000
6:70452568:ACAG:A	donor_loss	1.0000
6:70452569:CAG:C	donor_loss	1.0000
6:70452570:AG:A	donor_loss	1.0000
6:70452571:GGTA:G	donor_loss	1.0000
6:70452572:G:GA	donor_loss	1.0000
6:70452573:T:A	donor_loss	1.0000
6:70475658:TTCA:T	acceptor_loss	1.0000
6:70475659:TCA:T	acceptor_loss	1.0000
6:70475661:A:AG	acceptor_gain	1.0000
6:70475661:AGATT:A	acceptor_gain	1.0000
6:70475662:G:GT	acceptor_gain	1.0000
6:70475662:GA:G	acceptor_gain	1.0000
6:70475662:GAT:G	acceptor_gain	1.0000
6:70475662:GATT:G	acceptor_gain	1.0000
6:70475662:GATTG:G	acceptor_gain	1.0000
6:70475729:TATTC:T	donor_gain	1.0000

AlphaMissense

10050 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:70475709:T:C	L115P	1.000
6:70528426:T:C	L1250P	1.000
6:70528432:T:A	V1252D	1.000
6:70528443:G:C	G1256R	1.000
6:70528443:G:T	G1256C	1.000
6:70528444:G:A	G1256D	1.000
6:70528444:G:T	G1256V	1.000
6:70528447:T:C	L1257S	1.000
6:70528452:G:A	G1259R	1.000
6:70528452:G:C	G1259R	1.000
6:70533160:G:A	G1259E	1.000
6:70533160:G:T	G1259V	1.000
6:70533171:G:C	D1263H	1.000
6:70533172:A:C	D1263A	1.000
6:70533172:A:T	D1263V	1.000
6:70533175:T:A	L1264H	1.000
6:70533175:T:C	L1264P	1.000
6:70533766:T:C	F1293L	1.000
6:70533768:T:A	F1293L	1.000
6:70533768:T:G	F1293L	1.000
6:70533797:T:C	L1303P	1.000
6:70533853:A:C	S1322R	1.000
6:70536260:C:A	S1322R	1.000
6:70536260:C:G	S1322R	1.000
6:70536267:G:A	G1325R	1.000
6:70536267:G:C	G1325R	1.000
6:70536268:G:A	G1325E	1.000
6:70536279:G:C	G1329R	1.000
6:70536279:G:T	G1329C	1.000
6:70536280:G:A	G1329D	1.000

dbSNP variants (sampled 300 via entrez): RS1000002185 (6:70560959 G>A,T), RS1000013450 (6:70450945 G>A), RS1000065402 (6:70412842 T>G), RS1000086591 (6:70458514 A>G), RS1000093059 (6:70458012 T>G), RS1000095154 (6:70561319 C>T), RS1000123167 (6:70419036 T>G), RS1000129171 (6:70413868 C>T), RS1000149292 (6:70477702 A>C), RS1000170135 (6:70454380 T>C), RS1000180141 (6:70463177 C>G), RS1000196030 (6:70543137 C>T), RS1000232153 (6:70484567 A>G), RS1000237312 (6:70418556 C>T), RS1000238339 (6:70543165 A>G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:500000

GenCC curated gene-disease

Mondo (1): histiocytoid cardiomyopathy (MONDO:0010771)

Orphanet (1): Histiocytoid cardiomyopathy (Orphanet:137675)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012490_342	Femur bone mineral density x serum urate levels interaction	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535584	Cardiomyopathy, infantile histiocytoid (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	5
sodium arsenite	increases expression, decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Cisplatin	increases expression, affects cotreatment, decreases expression	2
Cyclosporine	increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
trichostatin A	increases expression	1
di-n-butylphosphoric acid	affects 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	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Vorinostat	affects expression	1
Acetaminophen	decreases expression	1
Atrazine	decreases expression	1
Caffeine	affects phosphorylation	1
Endosulfan	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Mercuric Chloride	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Phthalic Acids	decreases methylation	1
Quercetin	increases expression	1
Thimerosal	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Vanadates	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05658965	Not specified	RECRUITING	KIDSHEART AND BRAIN : Early EEG Surgery Congenital Heart Disease Predict Onset of Neurodevelopmental Disorders
NCT06818760	Not specified	RECRUITING	Remote Monitoring in Pregnant Women With Congenital Heart Disease Using Wrist Wearables
NCT07437261	Not specified	COMPLETED	Neuropsychomotor Development From Ages 6 to 18 in Children With Early Surgically Treated Congenital Heart Disease