FAM167A

Summary

FAM167A (family with sequence similarity 167 member A, HGNC:15549) is a protein-coding gene on chromosome 8p23.1, encoding Protein FAM167A (Q96KS9).

At a glance

• GWAS associations: 57
• Clinical variants (ClinVar): 69 total — 1 pathogenic
• MANE Select transcript: NM_053279

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15549
Approved symbol	FAM167A
Name	family with sequence similarity 167 member A
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	DIORA-1
Ensembl gene	ENSG00000154319
Ensembl biotype	protein_coding
OMIM	610085
Entrez	83648

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000284486, ENST00000527445, ENST00000528111, ENST00000528897, ENST00000531564, ENST00000531804, ENST00000534308, ENST00000648766, ENST00000872456, ENST00000872457, ENST00000872458, ENST00000942418

RefSeq mRNA: 1 — MANE Select: NM_053279 NM_053279

CCDS: CCDS5981

Canonical transcript exons

ENST00000284486 — 3 exons

Exon	Start	End
ENSE00001015271	11421476	11424636
ENSE00001286980	11466626	11466753
ENSE00002211221	11444031	11444808

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 91.13.

FANTOM5 (CAGE): breadth broad, TPM avg 3.8079 / max 149.7605, expressed in 883 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91846	2.2072	604
91847	0.5876	358
91852	0.5221	241
91850	0.1410	65
91848	0.1066	37
91849	0.0773	23
91853	0.0741	8
91845	0.0414	14
91855	0.0187	4
91854	0.0164	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	91.13	gold quality
islet of Langerhans	UBERON:0000006	89.98	gold quality
secondary oocyte	CL:0000655	89.64	gold quality
upper arm skin	UBERON:0004263	89.50	gold quality
oocyte	CL:0000023	88.23	gold quality
thyroid gland	UBERON:0002046	86.29	gold quality
left lobe of thyroid gland	UBERON:0001120	85.77	gold quality
right lobe of thyroid gland	UBERON:0001119	85.25	gold quality
amygdala	UBERON:0001876	84.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.39	gold quality
anterior cingulate cortex	UBERON:0009835	83.73	gold quality
right frontal lobe	UBERON:0002810	83.56	gold quality
caudate nucleus	UBERON:0001873	83.07	gold quality
pituitary gland	UBERON:0000007	82.75	gold quality
putamen	UBERON:0001874	82.48	gold quality
adenohypophysis	UBERON:0002196	82.24	gold quality
nucleus accumbens	UBERON:0001882	81.59	gold quality
temporal lobe	UBERON:0001871	81.36	gold quality
medial globus pallidus	UBERON:0002477	81.14	gold quality
upper leg skin	UBERON:0004262	80.31	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.22	gold quality
forebrain	UBERON:0001890	80.21	gold quality
hypothalamus	UBERON:0001898	80.17	gold quality
Ammon’s horn	UBERON:0001954	80.16	gold quality
ventricular zone	UBERON:0003053	79.91	gold quality
globus pallidus	UBERON:0001875	79.90	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.83	gold quality
primary visual cortex	UBERON:0002436	79.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.49	gold quality
neocortex	UBERON:0001950	79.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

103 targeting FAM167A, 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-6867-5P	100.00	82.21	3464
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-6748-5P	100.00	65.81	1057
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-5682	99.89	72.56	1005

Literature-anchored findings (GeneRIF, showing 16)

• identified and confirmed through replication two new genetic loci for SLE: a promoter-region allele associated with reduced expression of BLK and increased expression of C8orf13 and variants in the ITGAM-ITGAX region (PMID:18204098)
• Results indicate the FAM167A-BLK region may be a shared genetic factor for a number of autoimmune diseases in multiple populations, but the genetic contribution may be grater in Asian populations. (PMID:19740902)
• Our findings indicate that the rs13277113A allele is associated not only with SLE but also with SSc and that the FAM167A-BLK region is a common genetic risk factor for both SLE and SSc. (PMID:20131239)
• EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS. (PMID:20861858)
• These results confirm C8orf13-BLK as a systemic sclerosis risk locus (PMID:21480188)
• Strong correlations have been observed between TNFSF4, TNFAIP3 and FAM167A-BLK polymorphisms with primary Sjogren’s syndrome in Han Chinese.[FAM167A-BLK] (PMID:23635951)
• SNPs of the FAM167A-BLK region, but not the BANK1 SNPs, were associated with the development of primary Sjogren’s syndrome in Han Chinese. (PMID:23899688)
• The observations suggested that C8orf13-BLK, in combination with STAT4, plays a pivotal role in creating genetic susceptibility to polymyositis/dermatomyositis in Japanese individuals. (PMID:24632671)
• Results support previous findings that vaiants in the RHOB and FAM167A-BLK genes may be associated with susceptibility to systemic sclerosis. (PMID:25470816)
• the FAM167A-BLK polymorphisms were associated with Chinese PM/DM patients or these patients with ILD, indicating that PM/DM might share common gene with other autoimmune diseases. (PMID:25846585)
• SNPs in TNFSF4 and FAM167A-BLK may be involved in asthma and allergic rhinitis gene risk in the Han Chinese cohort. (PMID:27088737)
• current meta-analysis suggested that FAM167A-BLK rs2736340 polymorphism is associated with several autoimmune diseases (PMID:27105348)
• FAM167A gene is associated with several rheumatic diseases and encodes a novel disordered protein, DIORA-1, which is expressed highly in the lung, consistent with a potential role in disease pathogenesis (PMID:29663334)
• Our findings indicate a role for DIORA-1 in distinct B cell subsets, and suggest that DIORA-1 may contribute to the inflammatory process and disease pathogenesis in primary Sjogren’s syndrome through B cell involvement (PMID:30018071)
• Polymorphisms of FAM167A-BLK region confer risk of developing an autoimmune thyroid disease. (PMID:30351170)
• FAM167A is a key molecule to induce BCR-ABL-independent TKI resistance in CML via noncanonical NF-kappaB signaling activation. (PMID:35241148)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam167ab	ENSDARG00000023952
danio_rerio	fam167aa	ENSDARG00000067665
		ENSDARG00000103248
mus_musculus	Fam167a	ENSMUSG00000035095
rattus_norvegicus	Fam167a	ENSRNOG00000011316

Paralogs (3): FAM167B (ENSG00000183615), AARD (ENSG00000205002), C20orf202 (ENSG00000215595)

Protein

Protein identifiers

Protein FAM167A — Q96KS9 (reviewed: Q96KS9)

All UniProt accessions (3): Q96KS9, A0A3B3IU03, E9PIY0

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in skin, including primary keratinocytes, spleen, kidney, leukocytes, testis, lung, small intestine and prostate.

Similarity. Belongs to the FAM167 (SEC) family.

RefSeq proteins (1): NP_444509* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024280	FAM167	Family
IPR051771	FAM167_domain	Family

Pfam: PF11652

UniProt features (7 total): region of interest 2, sequence variant 2, chain 1, coiled-coil region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96KS9-F1	71.98	0.37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 111 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, BENPORATH_ES_WITH_H3K27ME3, CREBP1_Q2, BEIER_GLIOMA_STEM_CELL_DN, EFC_Q6, CREB_Q4, MODULE_206, ATTACAT_MIR3803P, CORRE_MULTIPLE_MYELOMA_UP, CREB_Q2_01, ATF4_Q2, RAAGNYNNCTTY_UNKNOWN, RFX1_01, GCM_USP6

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM167A	BLK	P51451	978
FAM167A	MTMR9	Q96QG7	871
FAM167A	XKR6	Q5GH73	743
FAM167A	MTMR7	Q9Y216	714
FAM167A	BANK1	Q8NDB2	664
FAM167A	PPP1R3B	Q86XI6	662
FAM167A	PXK	Q7Z7A4	608
FAM167A	IRF5	Q13568	583
FAM167A	PHRF1	Q9P1Y6	578
FAM167A	STAT4	Q14765	571
FAM167A	ITPKC	Q96DU7	559
FAM167A	TNIP1	Q15025	507
FAM167A	TNFSF4	P23510	504
FAM167A	TNPO3	Q9Y5L0	480
FAM167A	PTPN22	Q9Y2R2	478

IntAct

49 interactions, top by confidence:

A	B	Type	Score
GMCL1	FAM167A	psi-mi:“MI:0915”(physical association)	0.800
FAM167A	GMCL1	psi-mi:“MI:0915”(physical association)	0.800
POLR3GL	POLR3A	psi-mi:“MI:0914”(association)	0.730
FAM167A	PRPH	psi-mi:“MI:0915”(physical association)	0.670
FLJ13057	FAM167A	psi-mi:“MI:0915”(physical association)	0.560
FAM167A	FLJ13057	psi-mi:“MI:0915”(physical association)	0.560
DTNB	FAM167A	psi-mi:“MI:0915”(physical association)	0.560
TXLNB	FAM167A	psi-mi:“MI:0915”(physical association)	0.560
PPP3CA	FAM167A	psi-mi:“MI:0915”(physical association)	0.560
FAM167A	HIP1	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	FAM167A	psi-mi:“MI:0915”(physical association)	0.560
FAM167A	PRKCG	psi-mi:“MI:0915”(physical association)	0.560
PRPF40A	FAM167A	psi-mi:“MI:0915”(physical association)	0.560
FAM167A	COQ8A	psi-mi:“MI:0915”(physical association)	0.560
HTT	FAM167A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (141): FAM167A (Two-hybrid), CDC42BPG (Affinity Capture-MS), CNTRL (Affinity Capture-MS), NYNRIN (Affinity Capture-MS), CDC42BPA (Affinity Capture-MS), CEP250 (Affinity Capture-MS), PRPH (Affinity Capture-MS), CDC42BPB (Affinity Capture-MS), KIAA1598 (Affinity Capture-MS), CCDC18 (Affinity Capture-MS), CCDC122 (Affinity Capture-MS), CEP55 (Affinity Capture-MS), CEP44 (Affinity Capture-MS), MID1 (Affinity Capture-MS), NEFM (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: P17257, Q0V7M8, Q5RFZ7, Q6P1G6, Q96KS9, Q9BTA0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	60
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
12322	NC_000008.11:g.11474238G>A	Pathogenic

SpliceAI

735 predictions. Top by Δscore:

Variant	Effect	Δscore
8:11424632:TCCGT:T	acceptor_gain	1.0000
8:11424633:CCGT:C	acceptor_gain	1.0000
8:11424633:CCGTC:C	acceptor_gain	1.0000
8:11424634:CGTC:C	acceptor_gain	1.0000
8:11424637:C:CC	acceptor_gain	1.0000
8:11424634:CGT:C	acceptor_gain	0.9900
8:11424635:GT:G	acceptor_gain	0.9900
8:11424637:CT:C	acceptor_loss	0.9900
8:11446895:T:TA	donor_gain	0.9900
8:11466621:CCCA:C	donor_loss	0.9900
8:11446888:CAGGG:C	donor_gain	0.9800
8:11466628:T:A	donor_gain	0.9800
8:11466659:G:A	donor_gain	0.9800
8:11466680:T:TA	donor_gain	0.9800
8:11444807:CC:C	acceptor_gain	0.9700
8:11444808:CC:C	acceptor_gain	0.9700
8:11466677:T:TA	donor_gain	0.9600
8:11444807:CCCT:C	acceptor_loss	0.9300
8:11444809:C:CA	acceptor_loss	0.9300
8:11444810:T:C	acceptor_loss	0.9300
8:11446902:C:CA	donor_gain	0.9300
8:11466624:ACCTT:A	donor_gain	0.9300
8:11466625:CCTTC:C	donor_gain	0.9300
8:11444811:G:C	acceptor_loss	0.9200
8:11444206:G:A	donor_gain	0.9100
8:11466622:CCACC:C	donor_gain	0.9000
8:11466624:A:AC	donor_gain	0.8900
8:11466625:C:CC	donor_gain	0.8900
8:11444039:T:TA	donor_gain	0.8800
8:11466625:CCTT:C	donor_gain	0.8700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003922 (8:11446099 G>A), RS1000090828 (8:11423191 C>G), RS1000110956 (8:11438664 T>C), RS1000170057 (8:11430047 G>C), RS1000181690 (8:11439107 C>G,T), RS1000240860 (8:11429615 C>T), RS1000343785 (8:11462012 G>A), RS1000445769 (8:11433194 T>A), RS1000493163 (8:11436465 T>C), RS1000567137 (8:11432657 A>T), RS1000571089 (8:11457649 G>C,T), RS1000616636 (8:11466027 C>A), RS1000627947 (8:11453072 C>T), RS1000687691 (8:11466458 G>A,C,T), RS1000693909 (8:11428543 A>AG)

Disease associations

OMIM: gene MIM:610085 | disease phenotypes: MIM:613375

GenCC curated gene-disease

Mondo (1): maturity-onset diabetes of the young type 11 (MONDO:0013242)

Orphanet (1): MODY (Orphanet:552)

HPO phenotypes

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

GWAS associations

57 associations (top):

Study	Trait	p-value
GCST000144_1	Systemic lupus erythematosus	1.000000e-10
GCST001455_5	Kawasaki disease	8.000000e-21
GCST002337_17	Amyotrophic lateral sclerosis (sporadic)	1.000000e-06
GCST003103_2	Systemic lupus erythematosus	8.000000e-06
GCST003898_4	Cisplatin-induced ototoxicity	5.000000e-07
GCST004861_93	Itch intensity from mosquito bite	2.000000e-06
GCST005175_62	Coronary artery calcified atherosclerotic plaque (90 or 130 HU threshold) in type 2 diabetes	6.000000e-06
GCST005531_96	Multiple sclerosis	9.000000e-06
GCST005987_45	Albumin-globulin ratio	1.000000e-16
GCST005990_31	Non-albumin protein levels	1.000000e-15
GCST006052_6	Polymyositis	4.000000e-06
GCST006170_20	Systolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	6.000000e-10
GCST006192_32	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	9.000000e-08
GCST006192_66	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-08
GCST006195_10	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-07
GCST006195_58	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-08
GCST007709_194	General factor of neuroticism	9.000000e-11
GCST007709_228	General factor of neuroticism	2.000000e-08
GCST007709_229	General factor of neuroticism	2.000000e-08
GCST007709_55	General factor of neuroticism	1.000000e-11
GCST007709_78	General factor of neuroticism	9.000000e-13
GCST007709_85	General factor of neuroticism	2.000000e-12
GCST009131_14	Systemic sclerosis	3.000000e-21
GCST010002_269	Refractive error	1.000000e-24
GCST010132_11	Processed meat consumption	4.000000e-10
GCST010132_14	Processed meat consumption	2.000000e-15
GCST010132_15	Processed meat consumption	1.000000e-09
GCST010142_4	Fish- and plant-related diet	2.000000e-12
GCST010142_6	Fish- and plant-related diet	3.000000e-12
GCST010142_63	Fish- and plant-related diet	2.000000e-12

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0006951	ototoxicity
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0004723	coronary artery calcification
EFO:0005128	albumin:globulin ratio measurement
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement
EFO:0007660	neuroticism measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression	4
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression	3
Cyclosporine	affects expression, increases expression	3
Particulate Matter	increases expression, affects cotreatment, increases abundance	3
Cisplatin	affects expression, decreases expression	2
Estradiol	affects cotreatment, increases expression	2
Silicon Dioxide	decreases expression, affects expression	2
Smoke	increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
afuresertib	increases expression	1
chloroacetaldehyde	decreases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
bisphenol A	decreases expression	1
lead acetate	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
methylparaben	increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
abrine	increases expression	1
bisphenol S	increases methylation	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1

Clinical trials (associated diseases)

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