STKLD1

Summary

STKLD1 (serine/threonine kinase like domain containing 1, HGNC:28669) is a protein-coding gene on chromosome 9q34.2, encoding Serine/threonine kinase-like domain-containing protein STKLD1 (Q8NE28).

Predicted to enable protein serine/threonine kinase activity.

Source: NCBI Gene 169436 — RefSeq curated summary.

At a glance

• Gene–disease (curated): polydactyly (Limited, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 125 total
• MANE Select transcript: NM_153710

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28669
Approved symbol	STKLD1
Name	serine/threonine kinase like domain containing 1
Location	9q34.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC43306, SGK071
Ensembl gene	ENSG00000198870
Ensembl biotype	protein_coding
OMIM	618530
Entrez	169436

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000371957, ENST00000462310, ENST00000468046, ENST00000475232, ENST00000477284

RefSeq mRNA: 1 — MANE Select: NM_153710 NM_153710

CCDS: CCDS35169

Canonical transcript exons

ENST00000371957 — 18 exons

Exon	Start	End
ENSE00001245901	133404789	133404929
ENSE00001245908	133403920	133404048
ENSE00001245915	133403700	133403828
ENSE00001245922	133402878	133403012
ENSE00001245932	133401738	133401878
ENSE00001246026	133405252	133406096
ENSE00001819237	133376366	133376560
ENSE00003479402	133390681	133390796
ENSE00003482661	133379036	133379122
ENSE00003499410	133394291	133394409
ENSE00003545799	133387447	133387548
ENSE00003580620	133400413	133400529
ENSE00003596074	133395600	133395763
ENSE00003628970	133397972	133398055
ENSE00003643948	133383856	133383900
ENSE00003648357	133389526	133389596
ENSE00003656479	133385617	133385691
ENSE00003661814	133397164	133397294

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 87.46.

FANTOM5 (CAGE): breadth broad, TPM avg 0.3948 / max 25.0981, expressed in 185 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99269	0.3659	174
99270	0.0289	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	87.46	gold quality
left testis	UBERON:0004533	87.44	gold quality
testis	UBERON:0000473	86.74	gold quality
sural nerve	UBERON:0015488	85.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.25	gold quality
right frontal lobe	UBERON:0002810	77.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.06	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.06	gold quality
frontal cortex	UBERON:0001870	76.85	gold quality
primary visual cortex	UBERON:0002436	76.83	gold quality
prefrontal cortex	UBERON:0000451	76.69	gold quality
cerebral cortex	UBERON:0000956	76.50	gold quality
superior frontal gyrus	UBERON:0002661	76.47	gold quality
anterior cingulate cortex	UBERON:0009835	76.46	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	76.06	gold quality
temporal lobe	UBERON:0001871	75.73	gold quality
amygdala	UBERON:0001876	75.72	gold quality
Ammon’s horn	UBERON:0001954	75.54	gold quality
putamen	UBERON:0001874	74.48	gold quality
substantia nigra	UBERON:0002038	74.29	gold quality
brain	UBERON:0000955	74.23	gold quality
nucleus accumbens	UBERON:0001882	74.15	gold quality
cortical plate	UBERON:0005343	73.99	gold quality
hypothalamus	UBERON:0001898	73.27	gold quality
right hemisphere of cerebellum	UBERON:0014890	72.97	gold quality
lower esophagus mucosa	UBERON:0035834	72.91	gold quality
caudate nucleus	UBERON:0001873	72.86	gold quality
cerebellar hemisphere	UBERON:0002245	72.72	gold quality
cerebellar cortex	UBERON:0002129	72.71	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting STKLD1, 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-4533	100.00	69.48	2758
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-4274	98.59	66.10	630
HSA-MIR-193A-3P	98.59	66.36	769
HSA-MIR-193B-3P	98.59	66.62	748
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-6511A-5P	98.13	67.47	1770

Literature-anchored findings (GeneRIF, showing 1)

• Also known as SgK071, a unique kinase belonging to no group or family. Single orthologs have been found in other vertebrates and lower metazoans including Nematostella, but are absent from Drosophila and C. elegans. (PMID:12471243)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Stkld1	ENSMUSG00000049897
rattus_norvegicus	Stkld1	ENSRNOG00000027911

Protein

Protein identifiers

Serine/threonine kinase-like domain-containing protein STKLD1 — Q8NE28 (reviewed: Q8NE28)

Alternative names: Serine/threonine kinase-like domain-containing protein 1, Sugen kinase 071

All UniProt accessions (1): Q8NE28

UniProt curated annotations — full annotation on UniProt →

Domain organisation. The protein kinase domain is predicted to be catalytically inactive.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. STKL subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NE28-1	1	yes
Q8NE28-2	2
Q8NE28-3	3

RefSeq proteins (1): NP_714921* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily

Pfam: PF00069

UniProt features (13 total): splice variant 4, sequence variant 3, region of interest 2, binding site 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NE28-F1	82.64	0.48

Functional residue map

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

Ligand- & substrate-binding residues (2): 34–42; 57

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (1): protein phosphorylation (GO:0006468)

GO Molecular Function (4): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphorylation	1
protein modification process	1
protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1

Protein interactions and networks

STRING

396 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STKLD1	PAN3	Q58A45	517
STKLD1	PEAK1	Q9H792	497
STKLD1	SBK2	P0C263	479
STKLD1	PEAK3	Q6ZS72	453
STKLD1	KIAA0825	Q8IV33	429
STKLD1	FAM20A	Q96MK3	400
STKLD1	SELENOO	Q9BVL4	386
STKLD1	JAK1	P23458	385
STKLD1	ZNF141	Q15928	371
STKLD1	LMBR1	Q8WVP7	370
STKLD1	OBP2B	Q9NPH6	370
STKLD1	SRPK3	Q9UPE1	365
STKLD1	IQCE	Q6IPM2	351
STKLD1	MYBPHL	A2RUH7	349
STKLD1	CEP126	Q9P2H0	348

IntAct

5 interactions, top by confidence:

A	B	Type	Score
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
PSMD12	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMC3	PSMD12	psi-mi:“MI:0914”(association)	0.640

BioGRID (8): STKLD1 (Affinity Capture-MS), STKLD1 (Co-fractionation), STKLD1 (Co-fractionation), STKLD1 (Co-fractionation), STKLD1 (Affinity Capture-MS), STKLD1 (Affinity Capture-MS), STKLD1 (Affinity Capture-MS), STKLD1 (Affinity Capture-MS)

ESM2 similar proteins: A1IGU3, A1IGU4, A1IGU5, A5D8V7, A5PK16, A6QP29, A7E3N7, A8K8P3, A9CB34, B0KWR6, B5DFA1, D3ZI76, G3HQ82, O73770, P0C7M6, P41002, Q14129, Q14DK4, Q15051, Q3SYS7, Q3UK37, Q3UZY0, Q5SNV9, Q5SXM2, Q60953, Q60I26, Q60I27, Q69ZT1, Q6NUI2, Q8BP00, Q8BP86, Q8C1F5, Q8C2K1, Q8CJ00, Q8IV45, Q8NCU4, Q8NE28, Q8NEE8, Q8TE82, Q95KD7

Diamond homologs: A0A8I5ZNK2, D3ZBE5, G5ECN5, G5EEN4, G5EFU0, O23304, O76484, O88506, O95747, P28547, P38990, P83098, P9WI62, P9WI63, Q11112, Q3UUJ4, Q4R6X5, Q4U925, Q54Q69, Q551H4, Q5E9J9, Q5R495, Q5RBJ6, Q5ZK47, Q6P9R2, Q7RTN6, Q7TNZ6, Q7TYY6, Q863I2, Q8BYG9, Q8G4G1, Q8K4T3, Q8NE28, Q95QC4, Q9C0K7, Q9ES74, Q9ESG9, Q9UEW8, Q9Z1W9, B6F107

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	102
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3920 predictions. Top by Δscore:

Variant	Effect	Δscore
9:133379030:T:A	acceptor_gain	1.0000
9:133379033:TAGGT:T	acceptor_loss	1.0000
9:133379034:A:T	acceptor_loss	1.0000
9:133379119:GCAG:G	donor_gain	1.0000
9:133379122:GGTA:G	donor_loss	1.0000
9:133379123:G:GC	donor_loss	1.0000
9:133379124:T:A	donor_loss	1.0000
9:133390793:G:GT	donor_gain	1.0000
9:133390794:A:T	donor_gain	1.0000
9:133394406:GGAT:G	donor_gain	1.0000
9:133394407:GATG:G	donor_gain	1.0000
9:133394410:G:GG	donor_gain	1.0000
9:133395598:A:AG	acceptor_gain	1.0000
9:133395598:AG:A	acceptor_gain	1.0000
9:133395599:G:GA	acceptor_loss	1.0000
9:133395599:G:GG	acceptor_gain	1.0000
9:133395599:GG:G	acceptor_gain	1.0000
9:133395599:GGGC:G	acceptor_gain	1.0000
9:133395710:G:GT	donor_gain	1.0000
9:133395759:A:G	donor_gain	1.0000
9:133395759:ATAAA:A	donor_gain	1.0000
9:133395760:TAAA:T	donor_gain	1.0000
9:133395761:AAAG:A	donor_loss	1.0000
9:133395762:AAGT:A	donor_loss	1.0000
9:133395763:AG:A	donor_loss	1.0000
9:133395764:G:GG	donor_gain	1.0000
9:133395764:GTG:G	donor_loss	1.0000
9:133395765:T:A	donor_loss	1.0000
9:133397162:AG:A	acceptor_gain	1.0000
9:133397163:GG:G	acceptor_gain	1.0000

AlphaMissense

4466 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:133379119:G:C	K57N	0.993
9:133379119:G:T	K57N	0.993
9:133394359:T:A	W218R	0.992
9:133394359:T:C	W218R	0.992
9:133394308:T:A	W201R	0.991
9:133394308:T:C	W201R	0.991
9:133405317:T:C	F647L	0.987
9:133405319:C:A	F647L	0.987
9:133405319:C:G	F647L	0.987
9:133385671:T:C	F92L	0.984
9:133385673:C:A	F92L	0.984
9:133385673:C:G	F92L	0.984
9:133390690:A:C	K159N	0.982
9:133390690:A:T	K159N	0.982
9:133390686:T:A	L158H	0.980
9:133394361:G:C	W218C	0.980
9:133394361:G:T	W218C	0.980
9:133394353:G:C	D216H	0.979
9:133394368:G:C	G221R	0.979
9:133389572:T:C	L148P	0.978
9:133390699:C:A	N162K	0.978
9:133390699:C:G	N162K	0.978
9:133394369:G:A	G221D	0.978
9:133390742:A:C	S177R	0.976
9:133390744:T:A	S177R	0.976
9:133390744:T:G	S177R	0.976
9:133394354:A:C	D216A	0.975
9:133395751:G:C	R285P	0.975
9:133389592:C:G	H155D	0.974
9:133394338:T:C	F211L	0.974

dbSNP variants (sampled 300 via entrez): RS1000027809 (9:133375527 G>A,C), RS1000094615 (9:133374372 G>C), RS1000447742 (9:133398517 G>A), RS1000546467 (9:133399961 C>T), RS1000613058 (9:133398808 T>C), RS1000899095 (9:133388912 C>T), RS1000910768 (9:133389299 T>C), RS1000957074 (9:133380936 A>G), RS1001090397 (9:133395330 G>A), RS1001269497 (9:133380595 G>T), RS1001337394 (9:133375319 G>A), RS1001534794 (9:133391285 T>C), RS1001713237 (9:133403913 T>G), RS1001788613 (9:133375434 G>A), RS1001942951 (9:133378843 G>A)

Disease associations

OMIM: gene MIM:618530 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
polydactyly	Limited	Autosomal dominant

Mondo (1): polydactyly (MONDO:0021003)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001793_1	Coagulation factor levels	4.000000e-34
GCST001793_4	Coagulation factor levels	1.000000e-128
GCST010083_318	Hemoglobin levels	2.000000e-47
GCST010725_19	Malaria	9.000000e-11
GCST010725_31	Malaria	9.000000e-21
GCST010725_98	Malaria	1.000000e-19

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D017689	Polydactyly	C05.660.585.600; C16.131.621.585.600

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Other-unique family

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
afimoxifene	decreases response to substance	1
perfluorooctanoic acid	increases expression	1
aflatoxin B2	decreases methylation	1
perfluorooctane sulfonic acid	increases expression	1
perfluorohexanesulfonic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Testosterone	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001404	Not specified	COMPLETED	Phenotype and Etiology of Pallister-Hall Syndrome
NCT06239064	Not specified	ACTIVE_NOT_RECRUITING	Early Genetic Identification of Obesity