SACK1E

Summary

SACK1E (scaffolding CK1 anchoring protein E, HGNC:25972) is a protein-coding gene on chromosome 19q13.33, encoding Protein FAM83E (Q2M2I3). May play a role in MAPK signaling.

Enables protein kinase binding activity. Predicted to be involved in signal transduction.

Source: NCBI Gene 54854 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 137 total
• Druggable target: yes
• MANE Select transcript: NM_017708

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25972
Approved symbol	SACK1E
Name	scaffolding CK1 anchoring protein E
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20200
Ensembl gene	ENSG00000105523
Ensembl biotype	protein_coding
Entrez	54854

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000263266, ENST00000593772, ENST00000595110, ENST00000599126, ENST00000876133, ENST00000876134, ENST00000876135, ENST00000876136, ENST00000876137, ENST00000876138, ENST00000876139, ENST00000958243, ENST00000958244, ENST00000958245, ENST00000958246

RefSeq mRNA: 1 — MANE Select: NM_017708 NM_017708

CCDS: CCDS42587

Canonical transcript exons

ENST00000263266 — 7 exons

Exon	Start	End
ENSE00000717929	48612908	48614627
ENSE00000853323	48603494	48603911
ENSE00000853324	48609876	48610000
ENSE00000853325	48610680	48610847
ENSE00001242838	48599961	48601369
ENSE00003910206	48614937	48615076
ENSE00003911209	48614708	48614839

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 96.75.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2306 / max 26.3750, expressed in 101 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181870	0.1614	66
181871	0.0692	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	96.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.35	gold quality
rectum	UBERON:0001052	94.39	gold quality
gall bladder	UBERON:0002110	89.37	gold quality
minor salivary gland	UBERON:0001830	89.28	gold quality
transverse colon	UBERON:0001157	87.68	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.51	gold quality
right uterine tube	UBERON:0001302	86.32	gold quality
small intestine	UBERON:0002108	85.68	gold quality
saliva-secreting gland	UBERON:0001044	84.95	gold quality
upper lobe of left lung	UBERON:0008952	83.98	gold quality
mouth mucosa	UBERON:0003729	83.06	gold quality
upper lobe of lung	UBERON:0008948	82.67	gold quality
oocyte	CL:0000023	82.17	gold quality
duodenum	UBERON:0002114	82.14	gold quality
mucosa of stomach	UBERON:0001199	82.13	gold quality
body of stomach	UBERON:0001161	81.39	gold quality
secondary oocyte	CL:0000655	80.27	gold quality
nasal cavity epithelium	UBERON:0005384	80.17	silver quality
esophagus mucosa	UBERON:0002469	79.94	gold quality
lower esophagus mucosa	UBERON:0035834	79.84	gold quality
right lung	UBERON:0002167	79.27	gold quality
stomach	UBERON:0000945	79.13	gold quality
nasal cavity mucosa	UBERON:0001826	78.63	gold quality
colonic mucosa	UBERON:0000317	77.26	gold quality
bronchial epithelial cell	CL:0002328	77.09	silver quality
vermiform appendix	UBERON:0001154	77.04	gold quality
epithelium of bronchus	UBERON:0002031	77.03	silver quality
colonic epithelium	UBERON:0000397	76.84	gold quality
bronchus	UBERON:0002185	76.50	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting SACK1E, 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-6778-3P	99.96	67.29	2693
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-3670	97.88	64.39	763

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam83fa	ENSDARG00000038012
danio_rerio	fam83e	ENSDARG00000089489
danio_rerio	fam83fb	ENSDARG00000104188
mus_musculus	Fam83e	ENSMUSG00000054161
rattus_norvegicus	Fam83e	ENSRNOG00000021039

Paralogs (7): FAM83D (ENSG00000101447), FAM83C (ENSG00000125998), FAM83F (ENSG00000133477), FAM83A (ENSG00000147689), FAM83B (ENSG00000168143), FAM83H (ENSG00000180921), FAM83G (ENSG00000188522)

Protein

Protein identifiers

Protein FAM83E — Q2M2I3 (reviewed: Q2M2I3)

All UniProt accessions (2): Q2M2I3, M0QZ37

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in MAPK signaling.

Subunit / interactions. Directly interacts (via DUF1669) with CSNK1A1, CSNK1A1L, CSNK1D and CSNK1E. May interact with RAF1.

Subcellular location. Cytoplasm. Perinuclear region.

Domain organisation. All members of the FAM83 family of proteins share a conserved N-terminal DUF1669 (domain of unknown function 1669) domain of about 300 amino acids. This domain mediates the interaction with casein kinase 1 (CK1) isoforms. Therefore, it has been proposed to rename DUF1669 the polypeptide anchor of CK1 domain.

Similarity. Belongs to the FAM83 family.

RefSeq proteins (1): NP_060178* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012461	SACK1	Domain
IPR050944	FAM83	Family

Pfam: PF07894

UniProt features (15 total): region of interest 4, sequence conflict 3, sequence variant 3, mutagenesis site 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2M2I3-F1	70.31	0.46

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
243	decreased interaction with csnk1a1 and csnk1e.
277	decreased interaction with csnk1a1 and csnk1e.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 53 (showing top): RNCTGNYNRNCTGNY_UNKNOWN, GOMF_KINASE_BINDING, GSE13762_CTRL_VS_125_VITAMIND_DAY12_DC_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MIKKELSEN_ES_ICP_WITH_H3K4ME3, FEVR_CTNNB1_TARGETS_UP, BONOME_OVARIAN_CANCER_SURVIVAL_SUBOPTIMAL_DEBULKING, LEF1_UP.V1_DN, HOXC6_TARGET_GENES, KLF14_TARGET_GENES, KLF7_TARGET_GENES, MAFG_TARGET_GENES, SETD7_TARGET_GENES, SNRNP70_TARGET_GENES, SUPT16H_TARGET_GENES

GO Biological Process (1): signal transduction (GO:0007165)

GO Molecular Function (2): protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (2): perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
kinase binding	1
binding	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

296 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SACK1E	TRIM62	Q9BVG3	467
SACK1E	TTLL11	Q8NHH1	465
SACK1E	GUCA1B	Q9UMX6	457
SACK1E	ZNF362	Q5T0B9	456
SACK1E	ZSCAN20	P17040	454
SACK1E	KIF22	Q14807	445
SACK1E	TTBK2	Q6IQ55	444
SACK1E	DYNLL1	P63167	419
SACK1E	ZFP91	Q96JP5	414
SACK1E	LCN9	Q8WX39	412
SACK1E	GFI1B	Q5VTD9	410
SACK1E	HMMR	O75330	404
SACK1E	STOM	P27105	404
SACK1E	TTBK1	Q5TCY1	390
SACK1E	KCNT1	Q5JUK3	387

IntAct

7 interactions, top by confidence:

A	B	Type	Score
FAM83E	CSNK1A1	psi-mi:“MI:0914”(association)	0.540
FAM83E	CSNK1A1	psi-mi:“MI:0403”(colocalization)	0.540
FAM83E	CSNK1A1	psi-mi:“MI:0915”(physical association)	0.540

ESM2 similar proteins: A1L1C2, A2RRU4, A6QM06, A6QP75, E1BE10, E2RD63, G5E872, O75888, P29376, P70295, P97260, Q12770, Q1LZ97, Q28DT3, Q2M2I3, Q3TAA7, Q3U5Q7, Q3ZCA1, Q4FZD7, Q5EBM0, Q5MNU5, Q5SWZ9, Q60I26, Q60I27, Q69Z89, Q6AZ51, Q6GQT6, Q6IN84, Q6NUI2, Q6P9U1, Q7Z6J9, Q8BH06, Q8BTM9, Q8C0R7, Q8IYL2, Q8N1F8, Q8N2A8, Q8NAC3, Q8NFR9, Q8TDF6

Diamond homologs: A1L1G9, A2ARK0, A3KN19, A4QP72, A6ND36, A9JRM0, Q0VBM2, Q148V8, Q1LVV0, Q2M2I3, Q3UKU4, Q5SWY7, Q5T0W9, Q5XGY0, Q5XK72, Q66JF7, Q6PF42, Q6ZRV2, Q80XS7, Q86UY5, Q8K2P2, Q8NEG4, Q9BQN1, Q9D7I8, Q9H4H8, Q1RK58, Q4UJZ1, Q68VT0, Q9ZCD8

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
FAM83E	“up-regulates quantity”	CSNK1A1	binding
FAM83E	“up-regulates quantity”	CSNK1A1L	binding
FAM83E	“up-regulates quantity”	CSNK1E	binding
FAM83E	“up-regulates quantity”	CSNK1D	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	116
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1132 predictions. Top by Δscore:

Variant	Effect	Δscore
19:48601370:C:CC	acceptor_gain	1.0000
19:48603454:T:TA	donor_gain	1.0000
19:48610675:CCTA:C	donor_loss	1.0000
19:48610676:CTAC:C	donor_loss	1.0000
19:48610677:TACCT:T	donor_loss	1.0000
19:48610678:A:AT	donor_loss	1.0000
19:48610679:CCTCC:C	donor_loss	1.0000
19:48610681:T:TA	donor_gain	1.0000
19:48610794:C:CT	acceptor_gain	1.0000
19:48610844:CCAG:C	acceptor_gain	1.0000
19:48610845:CAGC:C	acceptor_gain	1.0000
19:48610848:C:CC	acceptor_gain	1.0000
19:48610854:A:C	acceptor_gain	1.0000
19:48601367:GAGC:G	acceptor_loss	0.9900
19:48601368:AGCT:A	acceptor_loss	0.9900
19:48601370:C:G	acceptor_loss	0.9900
19:48601371:T:A	acceptor_loss	0.9900
19:48603488:TCTCA:T	donor_loss	0.9900
19:48603489:CTCAC:C	donor_loss	0.9900
19:48603490:TCAC:T	donor_loss	0.9900
19:48603491:CACCT:C	donor_loss	0.9900
19:48603492:ACC:A	donor_loss	0.9900
19:48603493:C:CG	donor_loss	0.9900
19:48603912:C:CC	acceptor_gain	0.9900
19:48609756:CCCAT:C	acceptor_gain	0.9900
19:48609757:CCAT:C	acceptor_gain	0.9900
19:48609758:CAT:C	acceptor_gain	0.9900
19:48609760:T:TC	acceptor_gain	0.9900
19:48609997:CGTT:C	acceptor_gain	0.9900
19:48610000:TC:T	acceptor_loss	0.9900

AlphaMissense

3019 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:48603827:G:C	F281L	0.995
19:48603827:G:T	F281L	0.995
19:48603829:A:G	F281L	0.995
19:48603858:C:A	G271V	0.994
19:48603828:A:G	F281S	0.993
19:48603904:A:G	W256R	0.993
19:48603904:A:T	W256R	0.993
19:48603839:G:C	F277L	0.991
19:48603839:G:T	F277L	0.991
19:48603841:A:G	F277L	0.991
19:48609917:A:C	F239L	0.990
19:48609917:A:T	F239L	0.990
19:48609919:A:G	F239L	0.990
19:48603902:C:A	W256C	0.989
19:48603902:C:G	W256C	0.989
19:48612944:C:A	K143N	0.986
19:48612944:C:G	K143N	0.986
19:48613027:A:G	W116R	0.985
19:48613027:A:T	W116R	0.985
19:48610840:G:T	A158D	0.984
19:48603909:A:G	F254S	0.983
19:48603828:A:C	F281C	0.981
19:48609885:C:T	G250E	0.980
19:48609959:G:C	S225R	0.980
19:48609959:G:T	S225R	0.980
19:48609961:T:G	S225R	0.980
19:48610822:A:G	F164S	0.980
19:48603859:C:A	G271C	0.979
19:48610762:A:T	V184D	0.979
19:48603858:C:T	G271D	0.978

dbSNP variants (sampled 300 via entrez): RS1000240438 (19:48611143 G>T), RS1000291716 (19:48600305 C>T), RS1000583118 (19:48609864 C>T), RS1000942849 (19:48614096 A>C), RS1001027567 (19:48601874 G>A), RS1001030927 (19:48609670 A>C,G), RS1001058743 (19:48602344 G>A), RS1001364120 (19:48608445 T>A), RS1001432335 (19:48613330 C>A,G,T), RS1001482505 (19:48603219 A>G), RS1001497361 (19:48614451 T>C,G), RS1001530336 (19:48609130 G>A), RS1001847343 (19:48601694 G>A), RS1001939896 (19:48608319 C>A,T), RS1002227476 (19:48614911 G>A,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001241_6	Bipolar disorder	3.000000e-06
GCST002485_3	Elevated serum carcinoembryonic antigen levels	5.000000e-08
GCST010134_4	Non-oily fish consumption	3.000000e-16
GCST010135_4	Oily fish consumption	2.000000e-16
GCST010140_48	Pork consumption	2.000000e-16
GCST90002389_409	Lymphocyte percentage of white cells	9.000000e-36
GCST90002399_441	Neutrophil percentage of white cells	2.000000e-32
GCST90013406_97	Liver enzyme levels (alkaline phosphatase)	5.000000e-20

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005760	serum carcinoembryonic antigen measurement
EFO:0008111	diet measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067315 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.95	Kd	112.1	nM	CHEMBL3752910
6.85	ED50	141.4	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148367: Binding affinity to human FAM83E incubated for 45 mins by Kinobead based pull down assay	kd	0.1121	uM

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Lead	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Testosterone	increases expression, affects cotreatment	1
Valproic Acid	increases methylation	1
Copper Sulfate	increases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651409	Binding	Binding affinity to human FAM83E incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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