FAM3D

Summary

FAM3D (FAM3 metabolism regulating signaling molecule D, HGNC:18665) is a protein-coding gene on chromosome 3p14.2, encoding Protein FAM3D (Q96BQ1).

Predicted to enable cytokine activity. Involved in negative regulation of insulin secretion. Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 131177 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_138805

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18665
Approved symbol	FAM3D
Name	FAM3 metabolism regulating signaling molecule D
Location	3p14.2
Locus type	gene with protein product
Status	Approved
Aliases	EF7, OIT1
Ensembl gene	ENSG00000198643
Ensembl biotype	protein_coding
OMIM	608619
Entrez	131177

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 26 protein_coding, 1 nonsense_mediated_decay

ENST00000358781, ENST00000482623, ENST00000483787, ENST00000489857, ENST00000498347, ENST00000876434, ENST00000876435, ENST00000876436, ENST00000876437, ENST00000876438, ENST00000876439, ENST00000876440, ENST00000876441, ENST00000876442, ENST00000876443, ENST00000876444, ENST00000876445, ENST00000876446, ENST00000876447, ENST00000951607, ENST00000951608, ENST00000951609, ENST00000951610, ENST00000951611, ENST00000951612, ENST00000951613, ENST00000951614

RefSeq mRNA: 1 — MANE Select: NM_138805 NM_138805

CCDS: CCDS2893

Canonical transcript exons

ENST00000358781 — 10 exons

Exon	Start	End
ENSE00001009838	58636294	58636420
ENSE00001009839	58637141	58637225
ENSE00001077342	58653674	58653781
ENSE00001077343	58633946	58634368
ENSE00001077347	58666576	58666774
ENSE00001077349	58649315	58649338
ENSE00001398795	58655551	58655601
ENSE00003469252	58645509	58645626
ENSE00003469580	58640127	58640177
ENSE00003663772	58643662	58643720

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 99.58.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.4030 / max 660.4470, expressed in 86 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42743	0.7427	50
42747	0.5881	44
42748	0.4507	36
42742	0.4068	42
42744	0.0803	13
42746	0.0658	22
42745	0.0558	11
42741	0.0127	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.58	gold quality
mucosa of transverse colon	UBERON:0004991	99.43	gold quality
rectum	UBERON:0001052	99.39	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.92	gold quality
colonic mucosa	UBERON:0000317	98.84	gold quality
nasal cavity epithelium	UBERON:0005384	98.74	gold quality
ileal mucosa	UBERON:0000331	98.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.60	gold quality
parotid gland	UBERON:0001831	98.55	gold quality
trachea	UBERON:0003126	98.38	gold quality
nasal cavity mucosa	UBERON:0001826	98.32	gold quality
esophagus mucosa	UBERON:0002469	97.60	gold quality
pharyngeal mucosa	UBERON:0000355	97.41	gold quality
saliva-secreting gland	UBERON:0001044	97.31	gold quality
oral cavity	UBERON:0000167	96.90	gold quality
minor salivary gland	UBERON:0001830	96.90	gold quality
gall bladder	UBERON:0002110	96.77	gold quality
esophagus squamous epithelium	UBERON:0006920	96.69	gold quality
mouth mucosa	UBERON:0003729	95.74	gold quality
pylorus	UBERON:0001166	94.80	gold quality
pancreatic ductal cell	CL:0002079	93.92	silver quality
duodenum	UBERON:0002114	93.72	gold quality
buccal mucosa cell	CL:0002336	93.34	gold quality
palpebral conjunctiva	UBERON:0001812	92.82	gold quality
tonsil	UBERON:0002372	92.68	gold quality
superior surface of tongue	UBERON:0007371	92.61	gold quality
tongue	UBERON:0001723	92.58	gold quality
amniotic fluid	UBERON:0000173	92.55	gold quality
bronchus	UBERON:0002185	92.49	gold quality
bronchial epithelial cell	CL:0002328	92.25	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	1086.81
E-CURD-114	yes	710.38
E-CURD-88	yes	404.23
E-GEOD-125970	yes	44.70
E-HCAD-1	yes	12.04
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting FAM3D, 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-4282	99.99	75.36	6408
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-634	97.74	67.11	818
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-3620-5P	97.42	63.95	792
HSA-MIR-10400-3P	97.29	64.66	597
HSA-MIR-4674	97.29	64.62	597
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-1587	96.95	64.03	932
HSA-MIR-345-5P	96.40	66.43	663

Literature-anchored findings (GeneRIF, showing 7)

• A cytokine-like protein found in placenta (PMID:12160727)
• Statistical analysis indicated that six genes, NFATC2, SCP2, CACNA1C, TCRA, POLE, and FAM3D, were associated with narcolepsy. (PMID:20677014)
• Fam3D is a gut-derived protein that is expressed and secreted in a nutritional status-dependent manner (PMID:22226334)
• FAM3D plays a role in gastrointestinal homeostasis and inflammation through its receptors FPR1 and FPR2. (PMID:26966188)
• Targeting cytokine-like protein FAM3D lowers blood pressure in hypertension. (PMID:37301198)
• Hepatocyte-secreted FAM3D ameliorates hepatic steatosis by activating FPR1-hnRNP U-GR-SCAD pathway to enhance lipid oxidation. (PMID:37454871)
• DNA methylation-driven gene FAM3D promotes colorectal cancer growth via the ATF4-SESN2-mTORC1 pathway. (PMID:39388305)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fam3d	ENSMUSG00000021749
rattus_norvegicus	Fam3d	ENSRNOG00000007320
caenorhabditis_elegans		WBGENE00019786

Paralogs (3): FAM3A (ENSG00000071889), FAM3B (ENSG00000183844), FAM3C (ENSG00000196937)

Protein

Protein identifiers

Protein FAM3D — Q96BQ1 (reviewed: Q96BQ1)

All UniProt accessions (6): A0A0A8K9B4, C9IZW7, C9J5Z5, C9JB68, Q96BQ1, F8WCI4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Abundantly expressed in placenta and weakly expressed in small intestine.

Similarity. Belongs to the FAM3 family.

RefSeq proteins (1): NP_620160* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR039220	FAM3	Family
IPR039475	ILEI_FAM3C	Domain
IPR039477	ILEI/PANDER_dom	Domain

Pfam: PF15711

UniProt features (8 total): disulfide bond 2, sequence variant 2, signal peptide 1, chain 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96BQ1-F1	90.82	0.77

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 55–83, 61–218

Glycosylation sites (1): 107

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 121 (showing top): GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_INSULIN_SECRETION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION, GOBP_HORMONE_TRANSPORT, GOBP_ARTERY_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_CELL_CELL_SIGNALING, GOBP_AORTA_DEVELOPMENT, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_LEUKOCYTE_MIGRATION, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_ANTIGEN_PROCESSING_AND_PRESENTATION, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (6): neutrophil homeostasis (GO:0001780), positive regulation of macrophage antigen processing and presentation (GO:0002618), aorta development (GO:0035904), negative regulation of insulin secretion (GO:0046676), neutrophil migration (GO:1990266), signal transduction (GO:0007165)

GO Molecular Function (3): cytokine activity (GO:0005125), carbohydrate binding (GO:0030246), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
leukocyte homeostasis	1
myeloid cell homeostasis	1
macrophage antigen processing and presentation	1
positive regulation of antigen processing and presentation	1
regulation of macrophage antigen processing and presentation	1
artery development	1
insulin secretion	1
negative regulation of protein secretion	1
regulation of insulin secretion	1
negative regulation of peptide hormone secretion	1
granulocyte migration	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
receptor ligand activity	1

Protein interactions and networks

STRING

388 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM3D	FPR2	P25090	572
FAM3D	FPR1	P21462	559
FAM3D	GUF1	Q8N442	473
FAM3D	BPIFA1	Q9NP55	412
FAM3D	RAB11FIP1	Q6WKZ4	402
FAM3D	LCE5A	Q5TCM9	368
FAM3D	CRNN	Q9UBG3	333
FAM3D	TMPRSS11B	Q86T26	331
FAM3D	RARRES1	P49788	326
FAM3D	PRR15L	Q9BU68	324
FAM3D	OR4C46	A6NHA9	323
FAM3D	ZNF530	Q6P9A1	323
FAM3D	FAM107A	O95990	319
FAM3D	DENND10	Q8TCE6	285
FAM3D	TLCD2	A6NGC4	275

IntAct

5 interactions, top by confidence:

A	B	Type	Score
FAM3D	PKD2	psi-mi:“MI:0915”(physical association)	0.560
FAM3D	HSPA8	psi-mi:“MI:0915”(physical association)	0.400
FAM3D	CNN1	psi-mi:“MI:0914”(association)	0.350
FAM3D	PEX5	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): PKD2 (Affinity Capture-MS), PKD2 (Affinity Capture-MS), FAM3D (Proximity Label-MS), PKD2 (Affinity Capture-MS), CNN1 (Affinity Capture-MS), GLT8D1 (Affinity Capture-MS), DSCC1 (Affinity Capture-MS), PEX5 (Affinity Capture-MS), SPECC1L (Affinity Capture-MS), FAM3D (Co-fractionation), FAM3D (Co-fractionation)

ESM2 similar proteins: A0JNU3, A1L1F1, A2AIL4, A4IHH4, A4QP75, B3MGZ0, B4GGT6, F6ZFR0, O00746, O08776, O55137, O55171, O88202, O88267, P36776, P49753, P87355, Q28CM7, Q32LB9, Q330K2, Q3B8B2, Q3T056, Q4R816, Q4VK78, Q566Y1, Q58DL1, Q59HJ6, Q5EBA1, Q5RJV0, Q6DFN1, Q80YD1, Q810S1, Q86U10, Q8BWN8, Q8CGK3, Q8HY87, Q8NC60, Q924S5, Q96BQ1, Q99KK9

Diamond homologs: A5PKI3, B0BLS9, P58499, P97805, P98173, Q5R5C3, Q6GQC1, Q7ZYY4, Q810F4, Q8BI06, Q8WUJ3, Q91VU0, Q92520, Q96BQ1, Q9D309, Q9D8T0, Q5EAB6, Q5RCB9, Q5XIN7, Q8WZA1, Q91X88, P26572, P27115, P27808, Q09325, Q11068, Q9XGM8, A3KPQ7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1887 predictions. Top by Δscore:

Variant	Effect	Δscore
3:58634369:C:CC	acceptor_gain	1.0000
3:58636312:ACC:A	donor_gain	1.0000
3:58636313:CCC:C	donor_gain	1.0000
3:58636417:CATT:C	acceptor_gain	1.0000
3:58636419:TT:T	acceptor_gain	1.0000
3:58636421:C:CC	acceptor_gain	1.0000
3:58637133:CTACT:C	donor_loss	1.0000
3:58637134:TACTT:T	donor_loss	1.0000
3:58637135:ACTTA:A	donor_loss	1.0000
3:58637137:TTA:T	donor_loss	1.0000
3:58637138:TA:T	donor_loss	1.0000
3:58637139:A:AC	donor_gain	1.0000
3:58637140:C:CG	donor_gain	1.0000
3:58637223:CAT:C	acceptor_gain	1.0000
3:58637226:C:CC	acceptor_gain	1.0000
3:58645502:TAC:T	donor_loss	1.0000
3:58645503:ACT:A	donor_loss	1.0000
3:58645504:CT:C	donor_loss	1.0000
3:58645505:TTAC:T	donor_loss	1.0000
3:58645506:T:TG	donor_loss	1.0000
3:58645507:A:AC	donor_gain	1.0000
3:58645507:ACATG:A	donor_gain	1.0000
3:58645508:C:CC	donor_gain	1.0000
3:58645508:CATG:C	donor_gain	1.0000
3:58645508:CATGC:C	donor_gain	1.0000
3:58645625:CT:C	acceptor_gain	1.0000
3:58645627:C:CC	acceptor_gain	1.0000
3:58636345:G:C	donor_gain	0.9900
3:58636416:TCATT:T	acceptor_gain	0.9900
3:58636417:CATTC:C	acceptor_gain	0.9900

AlphaMissense

1488 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:58636344:A:G	W179R	0.999
3:58636344:A:T	W179R	0.999
3:58634327:C:A	W209C	0.998
3:58634327:C:G	W209C	0.998
3:58634329:A:G	W209R	0.998
3:58634329:A:T	W209R	0.998
3:58636342:C:A	W179C	0.998
3:58636342:C:G	W179C	0.998
3:58636352:C:G	R176P	0.998
3:58636378:A:C	S167R	0.998
3:58636378:A:T	S167R	0.998
3:58636380:T:G	S167R	0.998
3:58645556:A:C	S72R	0.998
3:58645556:A:T	S72R	0.998
3:58645558:T:G	S72R	0.998
3:58636349:T:A	D177V	0.997
3:58636354:G:C	F175L	0.997
3:58636354:G:T	F175L	0.997
3:58636356:A:G	F175L	0.997
3:58637156:T:A	D148V	0.997
3:58637157:C:G	D148H	0.997
3:58643678:G:C	N102K	0.997
3:58643678:G:T	N102K	0.997
3:58645533:G:T	P80H	0.997
3:58645554:C:T	G73E	0.997
3:58645555:C:A	G73W	0.997
3:58637165:G:T	A145D	0.996
3:58643682:A:G	L101P	0.996
3:58643685:C:A	G100V	0.996
3:58643686:C:G	G100R	0.996

dbSNP variants (sampled 300 via entrez): RS1000031450 (3:58651023 T>G), RS1000034674 (3:58642601 C>A), RS1000097837 (3:58634774 G>A), RS1000284070 (3:58656886 G>A), RS1000343914 (3:58663077 T>G), RS1000438816 (3:58662922 A>G), RS1000496654 (3:58668183 T>C), RS1000520383 (3:58665792 A>C), RS1000634524 (3:58657132 C>T), RS1000703721 (3:58635937 C>A), RS1000803360 (3:58641659 C>T), RS1000834799 (3:58641468 C>G,T), RS1000953044 (3:58667946 G>A), RS1001020860 (3:58659930 T>C), RS1001034628 (3:58652576 C>A,G,T)

Disease associations

OMIM: gene MIM:608619 | 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
GCST003542_43	Night sleep phenotypes	4.000000e-06
GCST006585_1319	Blood protein levels	3.000000e-18

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation	2
terbufos	increases methylation	1
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Arbutin	decreases expression	1
Fonofos	increases methylation	1
Methapyrilene	increases methylation	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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