FAM171A2

Summary

FAM171A2 (family with sequence similarity 171 member A2, HGNC:30480) is a protein-coding gene on chromosome 17q21.31, encoding Protein FAM171A2 (A8MVW0).

Predicted to be located in membrane.

Source: NCBI Gene 284069 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 120 total — 2 pathogenic
• MANE Select transcript: NM_198475

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30480
Approved symbol	FAM171A2
Name	family with sequence similarity 171 member A2
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	MGC34829
Ensembl gene	ENSG00000161682
Ensembl biotype	protein_coding
OMIM	621213
Entrez	284069

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000293443, ENST00000588067, ENST00000589407, ENST00000592560, ENST00000912942, ENST00000912943, ENST00000912944, ENST00000912945, ENST00000946728

RefSeq mRNA: 1 — MANE Select: NM_198475 NM_198475

CCDS: CCDS45701

Canonical transcript exons

ENST00000293443 — 8 exons

Exon	Start	End
ENSE00001135933	44353215	44355191
ENSE00001655295	44359579	44359671
ENSE00001706981	44355958	44356074
ENSE00001802441	44355715	44355841
ENSE00001899020	44363597	44363853
ENSE00003603885	44356173	44356352
ENSE00003638778	44359905	44360132
ENSE00003640902	44356430	44356588

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 97.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.3653 / max 320.5679, expressed in 1354 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166369	8.9445	1315
166368	1.4208	638

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.25	gold quality
ganglionic eminence	UBERON:0004023	94.76	gold quality
ventricular zone	UBERON:0003053	92.37	gold quality
kidney epithelium	UBERON:0004819	92.31	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.37	gold quality
left ventricle myocardium	UBERON:0006566	91.34	gold quality
upper arm skin	UBERON:0004263	88.47	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.84	gold quality
prefrontal cortex	UBERON:0000451	87.49	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.24	gold quality
cerebellar hemisphere	UBERON:0002245	87.19	gold quality
cerebellar cortex	UBERON:0002129	87.17	gold quality
right frontal lobe	UBERON:0002810	87.07	gold quality
cerebellum	UBERON:0002037	86.17	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.29	gold quality
anterior cingulate cortex	UBERON:0009835	85.22	gold quality
frontal cortex	UBERON:0001870	84.26	gold quality
neocortex	UBERON:0001950	84.24	gold quality
stromal cell of endometrium	CL:0002255	83.17	gold quality
epithelial cell of pancreas	CL:0000083	82.90	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.31	gold quality
nucleus accumbens	UBERON:0001882	81.07	gold quality
amygdala	UBERON:0001876	80.85	gold quality
cerebral cortex	UBERON:0000956	80.83	gold quality
vena cava	UBERON:0004087	80.81	gold quality
biceps brachii	UBERON:0001507	80.74	gold quality
brain	UBERON:0000955	79.84	gold quality
forebrain	UBERON:0001890	79.47	gold quality
vastus lateralis	UBERON:0001379	79.39	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	79.39	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.81

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• The FAM171A2 gene is a key regulator of progranulin expression and modifies the risk of multiple neurodegenerative diseases. (PMID:33087363)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam171a2a	ENSDARG00000075249
danio_rerio	fam171a2b	ENSDARG00000079656
mus_musculus	Fam171a2	ENSMUSG00000034685
rattus_norvegicus	Fam171a2	ENSRNOG00000021041

Paralogs (2): FAM171B (ENSG00000144369), FAM171A1 (ENSG00000148468)

Protein

Protein identifiers

Protein FAM171A2 — A8MVW0 (reviewed: A8MVW0)

All UniProt accessions (2): A8MVW0, K7EMG4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the FAM171 family.

RefSeq proteins (1): NP_940877* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018890	FAM171	Family
IPR048530	FAM171_N	Domain
IPR049175	FAM171_C	Domain

Pfam: PF10577, PF20771

UniProt features (23 total): compositionally biased region 6, region of interest 5, glycosylation site 4, modified residue 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8MVW0-F1	59.81	0.25

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 (3): 370, 372, 789

Glycosylation sites (4): 66, 201, 221, 265

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 21 (showing top): SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, ZNF592_TARGET_GENES, BLANCO_MELO_INFLUENZA_A_INFECTION_A594_CELLS_DN, GSE7568_CTRL_VS_24H_TGFB_TREATED_MACROPHAGES_WITH_IL4_AND_DEXAMETHASONE_DN, DESCARTES_MAIN_FETAL_SATB2_LRRC7_POSITIVE_CELLS, NR0B1_TARGET_GENES, GSE17974_IL4_AND_ANTI_IL12_VS_UNTREATED_4H_ACT_CD4_TCELL_DN, GSE19825_NAIVE_VS_IL2RALOW_DAY3_EFF_CD8_TCELL_UP, GSE19825_NAIVE_VS_IL2RAHIGH_DAY3_EFF_CD8_TCELL_UP, GSE19825_NAIVE_VS_DAY3_EFF_CD8_TCELL_UP, HE_LIM_SUN_FETAL_LUNG_C0_EARLY_MESOTHELIAL_CELL, GSE7400_CTRL_VS_CSF3_IN_VIVO_TREATED_PBMC_DN, GSE3203_WT_VS_IFNAR1_KO_INFLUENZA_INFECTED_LN_BCELL_DN, GSE22229_UNTREATED_VS_IMMUNOSUPP_THERAPY_RENAL_TRANSPLANT_PATIENT_PBMC_UP, GSE21927_EL4_VS_MCA203_TUMOR_MONOCYTES_DN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

506 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM171A2	ZNF696	Q9H7X3	406
FAM171A2	NPTX1	Q15818	395
FAM171A2	RNF141	Q8WVD5	371
FAM171A2	C5orf24	Q7Z6I8	370
FAM171A2	KRABD3	A5PL33	366
FAM171A2	BRINP2	Q9C0B6	349
FAM171A2	TNFRSF10D	Q9UBN6	349
FAM171A2	LRFN1	Q9P244	347
FAM171A2	NANP	Q8TBE9	345
FAM171A2	APMAP	Q9HDC9	335
FAM171A2	DCUN1D3	Q8IWE4	330
FAM171A2	AVPR1A	P37288	328
FAM171A2	NIPAL2	Q9H841	324
FAM171A2	ADGRA3	Q8IWK6	322
FAM171A2	SFT2D1	Q8WV19	321

IntAct

102 interactions, top by confidence:

A	B	Type	Score
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
P4HA3	FAM171A2	psi-mi:“MI:0914”(association)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
SLC39A5	TMEM223	psi-mi:“MI:0914”(association)	0.530
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
BTN2A1	POTEF	psi-mi:“MI:0914”(association)	0.530
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530
EFNB2	FAM171A2	psi-mi:“MI:0914”(association)	0.530
NCR3LG1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
FAM171B	FAM171A2	psi-mi:“MI:0914”(association)	0.530
BTNL3	FAM171A2	psi-mi:“MI:0914”(association)	0.530
JPH4	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
CD53	FAM171A2	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480

BioGRID (136): FAM171A2 (Two-hybrid), FAM171A2 (Two-hybrid), FAM171A2 (Affinity Capture-MS), FAM171A2 (Affinity Capture-MS), FAM171A2 (Affinity Capture-MS), FAM171A2 (Affinity Capture-MS), FAM171A2 (Affinity Capture-MS), FAM171A2 (Proximity Label-MS), FAM171A2 (Proximity Label-MS), FAM171A2 (Affinity Capture-MS), FAM171A2 (Affinity Capture-MS), FAM171A2 (Affinity Capture-MS), FAM171A2 (Affinity Capture-MS), FAM171A2 (Affinity Capture-MS), FAM171A2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RQ45, A0A0U1RQS6, A0A2R8YCJ5, A2A699, A2AEV7, A6NGB7, A6NJG2, A6NKF7, A6NKL6, A6NL88, A8MVW0, A9JSM3, B2RU40, B8ZZ34, C9JH25, D4A9R4, J3QNX5, P0CG09, P98077, Q0VD38, Q14761, Q17QH7, Q29RK8, Q2KJ18, Q2M3V2, Q3SX20, Q5BJT1, Q5HZJ5, Q5RKR3, Q5T442, Q64697, Q69YZ2, Q6PB97, Q6PCT2, Q6UXK2, Q6ZMQ8, Q6ZVH7, Q6ZW31, Q80XF7, Q8BLS7

Diamond homologs: A1L3I3, A2A699, A8MVW0, Q14CH0, Q5RD34, Q5RJX2, Q5VUB5, Q6P995

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 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
Activation of BAD and translocation to mitochondria	6	69.2×	3e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	61.1×	4e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	61.1×	4e-08
Activation of BH3-only proteins	6	45.1×	2e-07
RHO GTPases activate PKNs	6	28.8×	3e-06
Intrinsic Pathway for Apoptosis	6	26.6×	4e-06
FOXO-mediated transcription	5	25.4×	4e-05
EPH-ephrin mediated repulsion of cells	6	20.0×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	7	36.4×	3e-07
ephrin receptor signaling pathway	6	25.5×	2e-05
cell surface receptor protein tyrosine kinase signaling pathway	10	21.4×	3e-08
protein autophosphorylation	8	14.3×	2e-05
positive regulation of neuron projection development	7	11.8×	2e-04
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	10	9.7×	2e-05
positive regulation of MAPK cascade	9	9.0×	7e-05
axon guidance	7	7.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	114
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
4279220	GRCh37/hg19 17q21.31(chr17:42372068-42535002)x1	Pathogenic
98125	NM_002087.4(GRN):c.102del (p.Gly35fs)	Pathogenic

SpliceAI

1320 predictions. Top by Δscore:

Variant	Effect	Δscore
17:44355189:CTC:C	acceptor_gain	1.0000
17:44355190:TC:T	acceptor_gain	1.0000
17:44355190:TCC:T	acceptor_loss	1.0000
17:44355191:CC:C	acceptor_gain	1.0000
17:44355191:CCT:C	acceptor_loss	1.0000
17:44355192:C:CC	acceptor_gain	1.0000
17:44355192:CTGG:C	acceptor_loss	1.0000
17:44355710:CTCA:C	donor_loss	1.0000
17:44355711:TCA:T	donor_loss	1.0000
17:44355712:CACCG:C	donor_loss	1.0000
17:44355713:A:AC	donor_gain	1.0000
17:44355713:ACCGG:A	donor_gain	1.0000
17:44355714:C:CT	donor_gain	1.0000
17:44355714:CCGG:C	donor_gain	1.0000
17:44355714:CCGGC:C	donor_gain	1.0000
17:44355837:CAGCC:C	acceptor_gain	1.0000
17:44356070:CAGCC:C	acceptor_gain	1.0000
17:44356072:GCC:G	acceptor_gain	1.0000
17:44356073:CC:C	acceptor_gain	1.0000
17:44356073:CCC:C	acceptor_gain	1.0000
17:44356074:CC:C	acceptor_gain	1.0000
17:44356075:C:CC	acceptor_gain	1.0000
17:44356166:CACTT:C	donor_loss	1.0000
17:44356167:ACTT:A	donor_loss	1.0000
17:44356171:A:C	donor_loss	1.0000
17:44356172:C:G	donor_loss	1.0000
17:44356172:CCA:C	donor_gain	1.0000
17:44356172:CCACT:C	donor_gain	1.0000
17:44356349:TTGC:T	acceptor_gain	1.0000
17:44356350:TGC:T	acceptor_gain	1.0000

AlphaMissense

5214 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:44353778:C:A	W812C	1.000
17:44353778:C:G	W812C	1.000
17:44354208:G:A	S669F	1.000
17:44354249:G:C	F655L	1.000
17:44354249:G:T	F655L	1.000
17:44354250:A:C	F655C	1.000
17:44354250:A:G	F655S	1.000
17:44354251:A:G	F655L	1.000
17:44354254:A:G	W654R	1.000
17:44354254:A:T	W654R	1.000
17:44354589:A:G	I542T	1.000
17:44354589:A:T	I542N	1.000
17:44353745:G:C	F823L	0.999
17:44353745:G:T	F823L	0.999
17:44353746:A:G	F823S	0.999
17:44353747:A:G	F823L	0.999
17:44353780:A:G	W812R	0.999
17:44353780:A:T	W812R	0.999
17:44354202:A:T	I671N	0.999
17:44354206:A:C	Y670D	0.999
17:44354209:A:G	S669P	0.999
17:44354212:G:C	H668D	0.999
17:44354251:A:T	F655I	0.999
17:44354252:C:A	W654C	0.999
17:44354252:C:G	W654C	0.999
17:44354256:G:T	A653D	0.999
17:44354289:A:G	L642P	0.999
17:44354361:A:G	I618T	0.999
17:44354361:A:T	I618N	0.999
17:44354589:A:C	I542S	0.999

dbSNP variants (sampled 300 via entrez): RS1000581693 (17:44355168 T>TG), RS1000683038 (17:44358041 C>T), RS1000938518 (17:44361842 G>A), RS1001201403 (17:44357894 C>A,T), RS1001256828 (17:44358206 G>A), RS1001556908 (17:44353312 C>A,T), RS1001743027 (17:44360759 G>A), RS1001799029 (17:44353501 C>T), RS1002203880 (17:44356366 G>GT), RS1002208370 (17:44363227 G>A,C), RS1002257622 (17:44356629 G>A), RS1002409382 (17:44359231 C>G), RS1002559424 (17:44362934 G>C), RS1002886513 (17:44359248 C>T), RS1003142217 (17:44353343 G>T)

Disease associations

OMIM: gene MIM:621213 | disease phenotypes: MIM:607485, MIM:614706

GenCC curated gene-disease

Mondo (2): GRN-related frontotemporal lobar degeneration with Tdp43 inclusions (MONDO:0011842), neuronal ceroid lipofuscinosis 11 (MONDO:0013866)

Orphanet (4): Progressive non-fluent aphasia (Orphanet:100070), Frontotemporal dementia (Orphanet:282), CLN11 disease (Orphanet:314629), OBSOLETE: Adult neuronal ceroid lipofuscinosis (Orphanet:79262)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001337_52	Platelet count	2.000000e-08
GCST009325_55	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	1.000000e-11
GCST010703_292	Brain morphology (MOSTest)	1.000000e-14
GCST90026416_20	Mild age-related type 2 diabetes	8.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
daidzein	affects cotreatment, decreases expression	1
methyleugenol	increases expression	1
daidzin	affects cotreatment, decreases expression	1
sodium arsenite	decreases expression, increases abundance, affects cotreatment	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
genistin	affects cotreatment, decreases expression	1
glycitein	decreases expression, affects cotreatment	1
perfluoro-n-nonanoic acid	decreases expression	1
glycitin	affects cotreatment, decreases expression	1
abrine	decreases expression	1
bisphenol S	increases methylation	1
incobotulinumtoxinA	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases expression	1
Cisplatin	decreases expression	1
Endosulfan	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
N-Nitrosopyrrolidine	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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