SACK1F

Summary

SACK1F (scaffolding CK1 anchoring protein F, HGNC:25148) is a protein-coding gene on chromosome 22q13.1, encoding Protein FAM83F (Q8NEG4).

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

Source: NCBI Gene 113828 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 97 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_138435

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25148
Approved symbol	SACK1F
Name	scaffolding CK1 anchoring protein F
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000133477
Ensembl biotype	protein_coding
Entrez	113828

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000333407, ENST00000473717, ENST00000488874

RefSeq mRNA: 1 — MANE Select: NM_138435 NM_138435

CCDS: CCDS14000

Canonical transcript exons

ENST00000333407 — 5 exons

Exon	Start	End
ENSE00001323014	40029516	40043534
ENSE00001758504	39994954	39995531
ENSE00003679055	40019168	40019335
ENSE00003705031	40021290	40021963
ENSE00003709186	40019887	40020008

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 90.51.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6324 / max 67.3980, expressed in 380 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192395	1.6324	380

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	90.51	gold quality
right testis	UBERON:0004534	90.28	gold quality
ileal mucosa	UBERON:0000331	87.46	gold quality
sperm	CL:0000019	87.06	gold quality
testis	UBERON:0000473	86.37	gold quality
oviduct epithelium	UBERON:0004804	84.99	gold quality
mucosa of transverse colon	UBERON:0004991	84.91	gold quality
thymus	UBERON:0002370	83.96	gold quality
esophagus mucosa	UBERON:0002469	83.28	gold quality
lower esophagus mucosa	UBERON:0035834	82.41	gold quality
skin of abdomen	UBERON:0001416	81.49	gold quality
body of pancreas	UBERON:0001150	80.74	gold quality
skin of leg	UBERON:0001511	80.63	gold quality
zone of skin	UBERON:0000014	79.44	gold quality
parotid gland	UBERON:0001831	79.28	silver quality
buccal mucosa cell	CL:0002336	78.59	gold quality
pancreas	UBERON:0001264	78.48	gold quality
jejunal mucosa	UBERON:0000399	76.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.56	gold quality
islet of Langerhans	UBERON:0000006	76.19	gold quality
apex of heart	UBERON:0002098	75.51	gold quality
gingival epithelium	UBERON:0001949	74.92	silver quality
minor salivary gland	UBERON:0001830	74.70	gold quality
esophagus squamous epithelium	UBERON:0006920	74.58	silver quality
upper arm skin	UBERON:0004263	74.56	gold quality
gingiva	UBERON:0001828	74.45	silver quality
saliva-secreting gland	UBERON:0001044	74.43	gold quality
mouth mucosa	UBERON:0003729	74.19	gold quality
right lobe of thyroid gland	UBERON:0001119	72.62	gold quality
left lobe of thyroid gland	UBERON:0001120	72.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting SACK1F, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-6879-5P	97.77	65.52	1521

Literature-anchored findings (GeneRIF, showing 6)

• Results show that FAM83F expression was distinctly upregulated in non-small cell lung cancer (NSCLC) tissues. MiR-940 inhibited the proliferation of cancer cells by targeting FAM83F and further restrained the progression of NSCLC. (PMID:30280778)
• Low MiR-650 expression in glioma cells promotes tumor cell proliferation by up-regulating the expression of FAM83F. (PMID:30556880)
• Fam83F induces p53 stabilisation and promotes its activity. (PMID:30692643)
• MiR-1827 functions as a tumor suppressor in lung adenocarcinoma by targeting MYC and FAM83F. (PMID:31595558)
• FAM83F regulates canonical Wnt signalling through an interaction with CK1alpha. (PMID:33361109)
• Circ_0000735 enhances the proliferation, metastasis and glycolysis of non-small cell lung cancer by regulating the miR-635/FAM83F axis. (PMID:33560141)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam83fa	ENSDARG00000038012
danio_rerio	fam83e	ENSDARG00000089489
danio_rerio	fam83fb	ENSDARG00000104188
mus_musculus	Fam83f	ENSMUSG00000022408
rattus_norvegicus	Fam83f	ENSRNOG00000018330

Paralogs (7): FAM83D (ENSG00000101447), FAM83E (ENSG00000105523), FAM83C (ENSG00000125998), FAM83A (ENSG00000147689), FAM83B (ENSG00000168143), FAM83H (ENSG00000180921), FAM83G (ENSG00000188522)

Protein

Protein identifiers

Protein FAM83F — Q8NEG4 (reviewed: Q8NEG4)

All UniProt accessions (1): Q8NEG4

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Directly interacts (via DUF1669) with CSNK1A1 and CSNK1A1L.

Subcellular location. Cell membrane.

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NEG4-1	1	yes
Q8NEG4-2	2

RefSeq proteins (1): NP_612444* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012461	SACK1	Domain
IPR050944	FAM83	Family

Pfam: PF07894

UniProt features (21 total): sequence variant 4, region of interest 4, compositionally biased region 4, modified residue 3, mutagenesis site 2, initiator methionine 1, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEG4-F1	68.18	0.35

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): 2, 4, 479

Mutagenesis-validated functional residues (2):

Position	Phenotype
250	decreased interaction with csnk1a1.
284	decreased interaction with csnk1a1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 66 (showing top): AAAYRNCTG_UNKNOWN, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, NKX61_01, TGACATY_UNKNOWN, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, CHANDRAN_METASTASIS_UP, chr22q13, SMAD4_Q6, GOMF_KINASE_BINDING, YOSHIMURA_MAPK8_TARGETS_UP, CHEN_METABOLIC_SYNDROM_NETWORK, HATADA_METHYLATED_IN_LUNG_CANCER_UP, MEISSNER_NPC_HCP_WITH_H3K4ME2, MEISSNER_BRAIN_HCP_WITH_H3K4ME2, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN

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): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
kinase binding	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

224 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SACK1F	ZBTB39	O15060	507
SACK1F	ZNF98	A6NK75	447
SACK1F	ZNF653	Q96CK0	445
SACK1F	DTWD1	Q8N5C7	413
SACK1F	RNF166	Q96A37	398
SACK1F	FAM98C	Q17RN3	394
SACK1F	GZF1	Q9H116	390
SACK1F	CSNK1A1	P48729	367
SACK1F	ZFP91	Q96JP5	348
SACK1F	ZNF827	Q17R98	336
SACK1F	TSPAN19	P0C672	321
SACK1F	ZNF69	Q9UC07	321
SACK1F	SZRD1	Q7Z422	299
SACK1F	CRBN	Q96SW2	290
SACK1F	RAB28	P51157	269

IntAct

11 interactions, top by confidence:

A	B	Type	Score
FAM83F	CSNK1A1	psi-mi:“MI:0914”(association)	0.540
FAM83F	CSNK1A1	psi-mi:“MI:0915”(physical association)	0.540
CSNK1A1	FAM83F	psi-mi:“MI:0915”(physical association)	0.540
CSNK1A1	FAM83F	psi-mi:“MI:0403”(colocalization)	0.540
MME		psi-mi:“MI:0914”(association)	0.350
FAM83F	RBFOX3	psi-mi:“MI:0914”(association)	0.350
POTEC	FAM83B	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): FAM83F (Proximity Label-MS), FAM83F (Proximity Label-MS), FAM83F (Affinity Capture-MS), FAM83F (Affinity Capture-Western), CBWD3 (Affinity Capture-MS), RBFOX3 (Affinity Capture-MS), TUBB (Affinity Capture-MS), USP34 (Affinity Capture-MS), USP19 (Affinity Capture-MS), PPOX (Affinity Capture-MS), CCT6B (Affinity Capture-MS), PEX6 (Affinity Capture-MS), FAM83B (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), TUBA1A (Affinity Capture-MS)

ESM2 similar proteins: A1A4I4, A1A5B6, A4D2P6, B2DCZ9, B4F7F3, O00192, O08773, O08874, O08908, O35465, O43566, O62683, O75808, O95049, P70268, P97492, Q0QWG9, Q12851, Q14164, Q14318, Q16512, Q16513, Q3B7U9, Q3KR56, Q3MII6, Q3UFB7, Q5FVC2, Q60875, Q61161, Q63433, Q63788, Q6P5Z2, Q6PFQ7, Q6V7V2, Q6ZT62, Q7Z5H3, Q865S3, Q8BWW9, Q8IYK8, Q8K045

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

2 interactions.

A	Effect	B	Mechanism
FAM83F	“up-regulates quantity”	CSNK1A1	binding
FAM83F	“up-regulates quantity”	CSNK1A1L	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1042 predictions. Top by Δscore:

Variant	Effect	Δscore
22:40019165:CAGGT:C	acceptor_loss	1.0000
22:40019166:A:AG	acceptor_gain	1.0000
22:40019166:A:AT	acceptor_loss	1.0000
22:40019166:AG:A	acceptor_gain	1.0000
22:40019167:G:GG	acceptor_gain	1.0000
22:40019167:GG:G	acceptor_gain	1.0000
22:40019167:GGT:G	acceptor_gain	1.0000
22:40019167:GGTC:G	acceptor_gain	1.0000
22:40019167:GGTCA:G	acceptor_gain	1.0000
22:40019331:TTCGG:T	donor_gain	1.0000
22:40019332:TCGG:T	donor_gain	1.0000
22:40019333:CGG:C	donor_gain	1.0000
22:40019333:CGGGT:C	donor_loss	1.0000
22:40019334:GG:G	donor_gain	1.0000
22:40019334:GGG:G	donor_gain	1.0000
22:40019334:GGGTA:G	donor_loss	1.0000
22:40019335:GG:G	donor_gain	1.0000
22:40019335:GGT:G	donor_loss	1.0000
22:40019336:G:GG	donor_gain	1.0000
22:40019336:GTA:G	donor_loss	1.0000
22:40019881:CAACA:C	acceptor_loss	1.0000
22:40019884:CAGAA:C	acceptor_loss	1.0000
22:40019885:A:AC	acceptor_loss	1.0000
22:40019885:A:AG	acceptor_gain	1.0000
22:40019886:G:GG	acceptor_gain	1.0000
22:40019886:G:GT	acceptor_loss	1.0000
22:40019886:GA:G	acceptor_gain	1.0000
22:40019886:GAAC:G	acceptor_gain	1.0000
22:40020004:TACAG:T	donor_loss	1.0000
22:40020010:TGA:T	donor_loss	1.0000

AlphaMissense

3247 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:39995409:T:A	W123R	0.997
22:39995409:T:C	W123R	0.997
22:40019175:C:A	A166D	0.996
22:40021394:C:T	S295F	0.996
22:40021297:T:A	W263R	0.995
22:40021297:T:C	W263R	0.995
22:40021372:T:C	F288L	0.995
22:40021373:T:C	F288S	0.995
22:40021374:C:A	F288L	0.995
22:40021374:C:G	F288L	0.995
22:39995411:G:C	W123C	0.994
22:39995411:G:T	W123C	0.994
22:40019247:T:A	V190D	0.992
22:40019255:T:G	Y193D	0.992
22:40019894:G:C	R222P	0.992
22:40019900:G:C	R224P	0.992
22:40019965:T:C	F246L	0.992
22:40019967:C:A	F246L	0.992
22:40019967:C:G	F246L	0.992
22:39995361:T:C	Y107H	0.991
22:40019193:T:C	F172S	0.991
22:40019947:G:T	G240W	0.991
22:40019969:T:C	L247P	0.991
22:40021299:G:C	W263C	0.991
22:40021299:G:T	W263C	0.991
22:40019174:G:C	A166P	0.990
22:40019977:G:C	D250H	0.990
22:40019999:G:A	G257E	0.990
22:40021292:T:C	F261S	0.990
22:40021394:C:A	S295Y	0.990

dbSNP variants (sampled 300 via entrez): RS1000084727 (22:40028595 G>A), RS1000185687 (22:40027681 G>A), RS1000261142 (22:40025398 G>A), RS1000277988 (22:40017145 C>A), RS1000413418 (22:39995585 G>A,C), RS1000519114 (22:40024409 C>G), RS1000590443 (22:40025777 T>C), RS1000685869 (22:40029630 C>T), RS1000696405 (22:39994681 C>A), RS1000703350 (22:40027859 C>A), RS1000757537 (22:40029391 G>A), RS1000804355 (22:39995283 G>T), RS1000810319 (22:40038660 C>T), RS1000858130 (22:39994643 C>T), RS1000878376 (22:40043191 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): oligospermia (MONDO:0001913)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000798	Oligozoospermia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005951_24	Body mass index	2.000000e-08
GCST007565_21	Morning person	7.000000e-17
GCST010002_83	Refractive error	2.000000e-27

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008328	chronotype measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009845	Oligospermia	C12.100.500.430.508; C12.100.750.700.508; C12.200.294.430.508

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
Valproic Acid	increases expression, increases methylation	2
Cadmium Chloride	decreases expression	2
dimethylselenide	increases expression, increases oxidation	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation, decreases methylation	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
pomalidomide	decreases expression, increases degradation	1
Lenalidomide	increases degradation, decreases expression	1
Atrazine	increases expression	1
Methapyrilene	decreases methylation	1
Nicotine	increases expression	1
Ozone	increases expression, increases oxidation	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Aflatoxin B1	increases methylation	1
Hydroxyl Radical	increases expression, increases oxidation	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02307994	PHASE4	UNKNOWN	Clinical Research on Effectiveness and Safety of Treatment of Severe Oligospermia or Azoospermia With uFSH
NCT05320536	PHASE4	UNKNOWN	A Clinical Study of Gulingji Capsule in the Treatment of Idiopathic Oligospermia, Asthenia, and Teratozoospermia
NCT06260007	PHASE4	RECRUITING	Efficacy and Safety Study of Products Based on Tribulus Terrestris, L. in Men With Oligospermia
NCT00440180	PHASE3	TERMINATED	Aromatase Inhibitors in the Treatment of Male Infertility
NCT01409837	PHASE2	COMPLETED	The Effect and Safety of Lisinopril in Non-hypertensive Men With Infertility From Low Sperm Count
NCT02234206	PHASE2	COMPLETED	A Clinical Trial to Study the Safety and Efficacy of Chandrakanthi Choornam in Patients With Low Sperm Count
NCT07481370	PHASE2	ENROLLING_BY_INVITATION	Isotretinoin vs hCG for Male Infertility Due to Low or Absent Sperm
NCT05158114	PHASE1	WITHDRAWN	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for Testicular Injury and Oligospermia
NCT02063256	PHASE2/PHASE3	UNKNOWN	7 NUTS Study. Diet Modification and Male Fertility.
NCT06869863	PHASE1/PHASE2	RECRUITING	Study of Tolerability, Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of the Medicinal Product MediReg®
NCT00479960	EARLY_PHASE1	UNKNOWN	A Preliminary Study on Effect of Omega-3 on Human Sperm
NCT06342856	EARLY_PHASE1	UNKNOWN	Evaluation of Treatment With Coenzyme Q10 and L-Carnitine on Semen Parameters in Infertile Men With Idiopathic Oligoasthenoteratospermia
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT01239186	Not specified	COMPLETED	Identification and Characterization of the Methylation Abnormalities on Whole Genome Among Infertile Men
NCT01509482	Not specified	COMPLETED	Insulin Resistance in Idiopathic Oligospermia and Azoospermia
NCT01520584	Not specified	UNKNOWN	Supplement Intake in Infertile Men;the Effect on Sperm Parameters,Fertilization Rate and Embryo Quality
NCT01828710	Not specified	COMPLETED	Myo-inositol on Human Semen Parameters
NCT01856361	Not specified	TERMINATED	Ramipril for the Treatment of Oligospermia
NCT02155179	Not specified	COMPLETED	Sperm Pathology Samples and Morphokinetics
NCT03898752	Not specified	COMPLETED	Is Oxidative Stress in Semen Reduced by Lifestyle Intervention
NCT04349345	Not specified	COMPLETED	Seminal Fluid’s Changes Over 20 Years
NCT04795440	Not specified	COMPLETED	Comparison of ICSI Outcomes in Cycles Using Testicular and Ejaculate Sperm From Couples With High SDF
NCT05506722	Not specified	UNKNOWN	Using of Testes Shocker in Improving the Spermatogenesis and Sperms Activity
NCT05842239	Not specified	RECRUITING	Hyperbaric Oxygen Therapy for Men Suffering From Infertility Due to Oligospermia.
NCT06202469	Not specified	COMPLETED	Creatine and Ubiquinol for Sperm Quality
NCT07357701	Not specified	RECRUITING	Identifying Genome Variants in Non-Obstructive Azoospermia (NOA) or Primary Ovarian Insufficiency (POI)