SACK1G

Summary

SACK1G (scaffolding CK1 anchoring protein G, HGNC:32554) is a protein-coding gene on chromosome 17p11.2, encoding Protein FAM83G (A6ND36). Substrate for type I BMP receptor kinase involved in regulation of some target genes of the BMP signaling pathway.

Predicted to enable protein kinase binding activity. Involved in BMP signaling pathway. Located in cytosol and nucleus.

Source: NCBI Gene 644815 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary palmoplantar keratoderma (Limited, GenCC)
• Clinical variants (ClinVar): 190 total
• MANE Select transcript: NM_001039999

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32554
Approved symbol	SACK1G
Name	scaffolding CK1 anchoring protein G
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ41564, PAWS1
Ensembl gene	ENSG00000188522
Ensembl biotype	protein_coding
OMIM	615886
Entrez	644815

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000388995, ENST00000399096, ENST00000580115, ENST00000884590, ENST00000921601, ENST00000921602

RefSeq mRNA: 1 — MANE Select: NM_001039999 NM_001039999

CCDS: CCDS42276

Canonical transcript exons

ENST00000388995 — 6 exons

Exon	Start	End
ENSE00001504615	18977584	18978850
ENSE00001504616	18979549	18979673
ENSE00001536400	19004709	19004764
ENSE00001855506	18968789	18971748
ENSE00002709902	19003520	19004169
ENSE00003667191	18988247	18988414

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 94.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.7760 / max 117.6566, expressed in 1516 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164838	4.0694	1339
164837	2.1404	743
164839	0.5401	311
164836	0.0261	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	94.91	silver quality
gingival epithelium	UBERON:0001949	94.08	gold quality
skin of leg	UBERON:0001511	92.99	gold quality
gingiva	UBERON:0001828	92.33	gold quality
skin of abdomen	UBERON:0001416	92.24	gold quality
esophagus mucosa	UBERON:0002469	91.59	gold quality
lower esophagus mucosa	UBERON:0035834	91.42	gold quality
zone of skin	UBERON:0000014	91.07	gold quality
tendon of biceps brachii	UBERON:0008188	90.83	gold quality
right atrium auricular region	UBERON:0006631	84.47	gold quality
mucosa of transverse colon	UBERON:0004991	83.78	gold quality
right lobe of liver	UBERON:0001114	83.48	gold quality
pancreatic ductal cell	CL:0002079	82.93	silver quality
cardiac atrium	UBERON:0002081	82.91	gold quality
nipple	UBERON:0002030	82.34	gold quality
cartilage tissue	UBERON:0002418	82.30	gold quality
esophagus	UBERON:0001043	81.65	gold quality
epithelial cell of pancreas	CL:0000083	81.26	gold quality
ileal mucosa	UBERON:0000331	80.26	silver quality
mammalian vulva	UBERON:0000997	79.80	gold quality
buccal mucosa cell	CL:0002336	79.35	silver quality
esophagus squamous epithelium	UBERON:0006920	79.35	gold quality
body of stomach	UBERON:0001161	78.88	gold quality
pharyngeal mucosa	UBERON:0000355	78.79	gold quality
oral cavity	UBERON:0000167	78.78	gold quality
duodenum	UBERON:0002114	78.75	gold quality
liver	UBERON:0002107	78.72	gold quality
amniotic fluid	UBERON:0000173	78.07	gold quality
penis	UBERON:0000989	77.76	gold quality
upper leg skin	UBERON:0004262	77.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting SACK1G, 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-6727-3P	99.49	65.92	1333
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-1909-5P	98.94	64.01	484
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-3649	96.85	64.10	340

Literature-anchored findings (GeneRIF, showing 5)

• PAWS1 regulates the expression of some SMAD4-independent BMP target genes as well as some BMP-independent genes. (PMID:24554596)
• PAWS1 interacts in a dynamic fashion with the actin/cytoskeletal regulator CD2AP at lamellae, suggesting that its association with CD2AP controls actin organization and cellular migration. Genetic ablation of CD2AP from U2OS cells instigates actin and cell migration defects reminiscent of those seen in PAWS1-knockout cells. (PMID:29175910)
• PAWS1 interacts and co-localises with the alpha isoform of casein kinase 1 (CK1), and that PAWS1 mutations incapable of binding CK1 fail both to activate Wnt signalling and to elicit axis duplication in Xenopus embryos. (PMID:29514862)
• FAM83G Is a Novel Inducer of Apoptosis. (PMID:32570757)
• FAM83G promotes proliferation, invasion, and metastasis by regulating PI3K/AKT signaling in hepatocellular carcinoma cells. (PMID:34144502)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam83gb	ENSDARG00000062929
danio_rerio	fam83ga	ENSDARG00000090340
mus_musculus	Fam83g	ENSMUSG00000042377
rattus_norvegicus	Fam83g	ENSRNOG00000027924

Paralogs (7): FAM83D (ENSG00000101447), FAM83E (ENSG00000105523), FAM83C (ENSG00000125998), FAM83F (ENSG00000133477), FAM83A (ENSG00000147689), FAM83B (ENSG00000168143), FAM83H (ENSG00000180921)

Protein

Protein identifiers

Protein FAM83G — A6ND36 (reviewed: A6ND36)

Alternative names: Protein associated with SMAD1

All UniProt accessions (2): A6ND36, K7EKG0

UniProt curated annotations — full annotation on UniProt →

Function. Substrate for type I BMP receptor kinase involved in regulation of some target genes of the BMP signaling pathway. Also regulates the expression of several non-BMP target genes, suggesting a role in other signaling pathways.

Subunit / interactions. Interacts with SMAD1 (via MH2 domain); in a SMAD4-independent manner. Directly interacts (via DUF1669) with casein kinase isoforms CSNK1A1 and CSNK1A1L.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Post-translational modifications. Phosphorylated in vitro by CSNK1A1. BMP signaling induces the phosphorylation by BMPR1A at Ser-610, Ser-614 and Ser-616. Phosphorylation at Ser-610 is necessary for the activation of SMAD4-independent BMP target genes such as NEDD9 and ASNS.

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?
A6ND36-1	1	yes
A6ND36-2	2

RefSeq proteins (1): NP_001035088* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012461	SACK1	Domain
IPR050944	FAM83	Family

Pfam: PF07894

UniProt features (31 total): modified residue 10, compositionally biased region 6, splice variant 4, region of interest 3, sequence variant 3, mutagenesis site 3, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6ND36-F1	59.85	0.24

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 (10): 2, 4, 124, 127, 356, 610, 614, 616, 650, 666

Mutagenesis-validated functional residues (3):

Position	Phenotype
296	loss of interaction with csnk1a1. loss of interaction with csnk1a1; when associated with a-300.
300	no effect on interaction with csnk1a1. loss of interaction with csnk1a1; when associated with a-296.
610	completely abolishes phosphorylation by alk3 in vitro. nedd9 and asns activation in response to bmps is abolished.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 68 (showing top): MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOBP_RESPONSE_TO_BMP, GOBP_RESPONSE_TO_GROWTH_FACTOR, DURCHDEWALD_SKIN_CARCINOGENESIS_DN, SANSOM_APC_MYC_TARGETS, GOMF_KINASE_BINDING, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MEISSNER_BRAIN_HCP_WITH_H3K4ME2_AND_H3K27ME3, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, BRUINS_UVC_RESPONSE_LATE, FEVR_CTNNB1_TARGETS_UP, ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF, GOBP_ENZYME_LINKED_RECEPTOR_PROTEIN_SIGNALING_PATHWAY, NAB2_TARGET_GENES

GO Biological Process (1): BMP signaling pathway (GO:0030509)

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

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
kinase binding	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

288 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SACK1G	CSNK1A1	P48729	476
SACK1G	CRBN	Q96SW2	462
SACK1G	SLC5A10	A0PJK1	418
SACK1G	TNK2	Q07912	415
SACK1G	GRAPL	Q8TC17	377
SACK1G	PDILT	Q8N807	355
SACK1G	LGMN	Q99538	350
SACK1G	CSNK1E	P49674	323
SACK1G	C3orf70	A6NLC5	321
SACK1G	FAM110A	Q9BQ89	312
SACK1G	TCFL5	Q9UL49	306
SACK1G	TACC2	O95359	302
SACK1G	GFOD2	Q3B7J2	291
SACK1G	CSNK1G1	Q9HCP0	290
SACK1G	GLDN	Q6ZMI3	288

IntAct

57 interactions, top by confidence:

A	B	Type	Score
FAM83G	CSNK1A1	psi-mi:“MI:0914”(association)	0.900
FAM83G	CSNK1A1	psi-mi:“MI:0915”(physical association)	0.900
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
CSNK1A1	FAM83G	psi-mi:“MI:0403”(colocalization)	0.900
CSNK1A1	FAM83G	psi-mi:“MI:0217”(phosphorylation reaction)	0.900
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
YWHAH	FAM83G	psi-mi:“MI:0914”(association)	0.710
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530

BioGRID (42): FAM83G (Affinity Capture-RNA), FAM83G (Affinity Capture-RNA), FAM83G (Affinity Capture-MS), FAM83G (Affinity Capture-MS), FAM83G (Affinity Capture-MS), FAM83G (Affinity Capture-MS), FAM83G (Affinity Capture-MS), FAM83G (Affinity Capture-MS), FAM83G (Affinity Capture-MS), FAM83G (Affinity Capture-RNA), FAM83G (Proximity Label-MS), FAM83G (Proximity Label-MS), FAM83G (Affinity Capture-Western), FAM83G (Affinity Capture-MS), FAM83G (Affinity Capture-MS)

ESM2 similar proteins: A0JPN4, A2A288, A2ARK0, A6ND36, A6QQJ8, A7E316, E9Q0S6, E9Q2Z1, O15037, O54714, O54967, O70260, O70405, O75385, O94983, P42335, P48778, Q07912, Q0P4K8, Q17R13, Q1LVK9, Q32PJ7, Q4V8I3, Q5D1E7, Q5D1E8, Q5DTV4, Q5HYM0, Q5JV73, Q5SWY7, Q5SXM2, Q5U2X5, Q5XIS1, Q68CZ2, Q6A037, Q6IRU7, Q6P1H6, Q6S5L8, Q7TP65, Q7TSG2, Q80U38

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

7 interactions.

A	Effect	B	Mechanism
BMPR1A	“up-regulates activity”	FAM83G	phosphorylation
FAM83G	“up-regulates activity”	CD2AP	binding
FAM83G	“up-regulates quantity”	CSNK1A1	binding
FAM83G	“up-regulates quantity”	CSNK1A1L	binding
PRKD1	“up-regulates activity”	FAM83G	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	8	199.0×	2e-15
Activation of BAD and translocation to mitochondria	7	197.4×	1e-13
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	174.2×	2e-13
Activation of BH3-only proteins	7	128.7×	2e-12
FOXO-mediated transcription	7	87.1×	3e-11
RHO GTPases activate PKNs	7	82.2×	4e-11
Intrinsic Pathway for Apoptosis	7	75.9×	7e-11
SARS-CoV-1-host interactions	8	52.1×	4e-11

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	65.4×	2e-06
intracellular protein localization	8	29.9×	5e-08
protein phosphorylation	5	12.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	162
Likely benign	17
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2194 predictions. Top by Δscore:

Variant	Effect	Δscore
17:18969046:CCGCA:C	acceptor_loss	1.0000
17:18969047:CGCA:C	acceptor_loss	1.0000
17:18969048:GCA:G	acceptor_loss	1.0000
17:18969049:CA:C	acceptor_loss	1.0000
17:18969050:A:AG	acceptor_gain	1.0000
17:18969050:AGCT:A	acceptor_gain	1.0000
17:18969050:AGCTG:A	acceptor_gain	1.0000
17:18969051:G:GT	acceptor_gain	1.0000
17:18969051:GC:G	acceptor_gain	1.0000
17:18969051:GCT:G	acceptor_gain	1.0000
17:18969051:GCTG:G	acceptor_gain	1.0000
17:18969051:GCTGG:G	acceptor_gain	1.0000
17:18969153:CGCAG:C	donor_loss	1.0000
17:18969154:GCAGG:G	donor_loss	1.0000
17:18969155:CAGGT:C	donor_loss	1.0000
17:18969156:AG:A	donor_loss	1.0000
17:18969157:GGT:G	donor_loss	1.0000
17:18969158:GTAT:G	donor_loss	1.0000
17:18969159:T:A	donor_loss	1.0000
17:18971001:T:TA	acceptor_gain	1.0000
17:18971009:CCAG:C	acceptor_loss	1.0000
17:18971010:CAGCT:C	acceptor_loss	1.0000
17:18971011:A:AG	acceptor_gain	1.0000
17:18971012:G:GG	acceptor_gain	1.0000
17:18971012:GC:G	acceptor_gain	1.0000
17:18971012:GCT:G	acceptor_gain	1.0000
17:18971012:GCTT:G	acceptor_gain	1.0000
17:18971012:GCTTT:G	acceptor_gain	1.0000
17:18971217:AGGT:A	donor_loss	1.0000
17:18971218:GGT:G	donor_loss	1.0000

AlphaMissense

5385 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:18978843:A:G	W275R	1.000
17:18978843:A:T	W275R	1.000
17:19003545:C:G	R166P	0.999
17:19003556:T:A	K162N	0.999
17:19003556:T:G	K162N	0.999
17:19003557:T:A	K162I	0.999
17:19003639:A:G	W135R	0.999
17:19003639:A:T	W135R	0.999
17:18978426:A:G	W414R	0.998
17:18978426:A:T	W414R	0.998
17:18978797:C:T	G290D	0.998
17:18978841:C:A	W275C	0.998
17:18978841:C:G	W275C	0.998
17:18988362:A:G	L192P	0.998
17:18988389:A:G	F183S	0.998
17:18988407:G:T	A177D	0.998
17:19003596:A:T	V149D	0.998
17:19003605:C:G	R146P	0.998
17:19003868:G:C	F58L	0.998
17:19003868:G:T	F58L	0.998
17:19003870:A:G	F58L	0.998
17:19003967:G:C	F25L	0.998
17:19003967:G:T	F25L	0.998
17:19003969:A:G	F25L	0.998
17:18978387:C:G	G427R	0.997
17:18978797:C:A	G290V	0.997
17:18978798:C:G	G290R	0.997
17:18978803:A:G	L288P	0.997
17:18979610:C:G	G252R	0.997
17:18979638:G:C	F242L	0.997

dbSNP variants (sampled 300 via entrez): RS1000017554 (17:18979405 CG>C), RS1000108166 (17:19005577 G>C), RS1000119288 (17:18982264 C>G), RS1000156355 (17:18968490 G>A), RS1000190467 (17:18982965 G>A), RS1000305407 (17:19006343 C>G,T), RS1000423531 (17:18968662 C>G), RS1000459233 (17:18972523 G>A), RS1000636305 (17:19006672 A>C), RS1000646916 (17:18972150 C>T), RS1000723558 (17:18983172 C>G,T), RS1000737661 (17:18974133 C>T), RS1000995333 (17:19004734 G>C,T), RS1001024967 (17:19007915 G>A), RS1001079488 (17:19001264 G>T)

Disease associations

OMIM: gene MIM:615886 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary palmoplantar keratoderma	Limited	Autosomal recessive

Mondo (1): hereditary palmoplantar keratoderma (MONDO:0019272)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects cotreatment	3
Estradiol	increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	decreases methylation	1
cupric chloride	increases expression	1
epigallocatechin gallate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
abrine	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Cisplatin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methapyrilene	decreases methylation	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	decreases methylation, increases methylation	1

Clinical trials (associated diseases)

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