SP9

gene
On this page

Also known as ZNF990

Summary

SP9 (Sp9 transcription factor, HGNC:30690) is a protein-coding gene on chromosome 2q31.1, encoding Transcription factor Sp9 (P0CG40). Transcription factor which plays a key role in limb development.

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in chromatin.

Source: NCBI Gene 100131390 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
  • Clinical variants (ClinVar): 58 total — 4 pathogenic, 2 likely-pathogenic
  • MANE Select transcript: NM_001145250

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:30690
Approved symbolSP9
NameSp9 transcription factor
Location2q31.1
Locus typegene with protein product
StatusApproved
AliasesZNF990
Ensembl geneENSG00000217236
Ensembl biotypeprotein_coding
OMIM621003
Entrez100131390

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000394967

RefSeq mRNA: 1 — MANE Select: NM_001145250 NM_001145250

CCDS: CCDS46453

Canonical transcript exons

ENST00000394967 — 2 exons

ExonStartEnd
ENSE00001559933174334954174335113
ENSE00001560331174336107174338500

Expression profiles

Bgee: expression breadth broad, 44 present calls, max score 88.52.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8502 / max 96.9834, expressed in 197 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
237900.6013147
237910.2489104

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047388.52gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099187.82gold quality
ganglionic eminenceUBERON:000402369.89gold quality
putamenUBERON:000187468.38gold quality
prefrontal cortexUBERON:000045168.19gold quality
nucleus accumbensUBERON:000188268.08gold quality
caudate nucleusUBERON:000187367.70gold quality
anterior cingulate cortexUBERON:000983567.44gold quality
superior frontal gyrusUBERON:000266165.60gold quality
Brodmann (1909) area 9UBERON:001354064.47gold quality
frontal cortexUBERON:000187064.42gold quality
ventricular zoneUBERON:000305364.41gold quality
dorsolateral prefrontal cortexUBERON:000983464.38gold quality
temporal lobeUBERON:000187164.37gold quality
amygdalaUBERON:000187664.22gold quality
stromal cell of endometriumCL:000225564.17gold quality
cerebral cortexUBERON:000095663.54gold quality
primary visual cortexUBERON:000243663.02gold quality
cortical plateUBERON:000534362.61gold quality
right frontal lobeUBERON:000281058.74gold quality
Ammon’s hornUBERON:000195456.49gold quality
hypothalamusUBERON:000189856.22gold quality
bone marrow cellCL:000209255.25gold quality
brainUBERON:000095554.47gold quality
colonic epitheliumUBERON:000039753.32gold quality
skin of abdomenUBERON:000141651.50gold quality
substantia nigraUBERON:000203849.48gold quality
fallopian tubeUBERON:000388947.91gold quality
right uterine tubeUBERON:000130247.03gold quality
placentaUBERON:000198745.21gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-HCAD-5yes18.99
E-MTAB-8894no469.01
E-ANND-3no0.33

Regulation

Is transcription factor: yes

JASPAR motifs

MotifNameFamily
MA1564.1SP9Three-zinc finger Kruppel-related
MA1564.2SP9Three-zinc finger Kruppel-related

JASPAR matrix evidence (PMIDs): PMID:26187067

Literature-anchored findings (GeneRIF, showing 1)

  • De novo variants in SP9 cause a novel form of interneuronopathy characterized by intellectual disability, autism spectrum disorder, and epilepsy with variable expressivity. (PMID:38288683)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_reriosp9ENSDARG00000099374
mus_musculusSp9ENSMUSG00000068859
rattus_norvegicusSp9ENSRNOG00000028187
drosophila_melanogasterlunaFBGN0040765

Paralogs (22): KLF6 (ENSG00000067082), KLF8 (ENSG00000102349), KLF5 (ENSG00000102554), KLF1 (ENSG00000105610), KLF3 (ENSG00000109787), KLF7 (ENSG00000118263), KLF12 (ENSG00000118922), KLF9 (ENSG00000119138), KLF2 (ENSG00000127528), KLF16 (ENSG00000129911), KLF4 (ENSG00000136826), KLF10 (ENSG00000155090), KLF15 (ENSG00000163884), SP8 (ENSG00000164651), KLF13 (ENSG00000169926), SP7 (ENSG00000170374), KLF17 (ENSG00000171872), KLF11 (ENSG00000172059), SP6 (ENSG00000189120), SP5 (ENSG00000204335), KLF14 (ENSG00000266265), KLF18 (ENSG00000283039)

Protein

Protein identifiers

Transcription factor Sp9P0CG40 (reviewed: P0CG40)

All UniProt accessions (1): P0CG40

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor which plays a key role in limb development. Positively regulates FGF8 expression in the apical ectodermal ridge (AER) and contributes to limb outgrowth in embryos.

Subcellular location. Nucleus.

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In SP9, the motif is inactive.

Similarity. Belongs to the Sp1 C2H2-type zinc-finger protein family.

RefSeq proteins (1): NP_001138722* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR013087Znf_C2H2_typeDomain
IPR036236Znf_C2H2_sfHomologous_superfamily

Pfam: PF00096

UniProt features (7 total): zinc finger region 3, chain 1, region of interest 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P0CG40-F149.040.00

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 (1): 440

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 21 (showing top): GOBP_APPENDAGE_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOBP_EMBRYONIC_MORPHOGENESIS, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, GOBP_APPENDAGE_MORPHOGENESIS, GOBP_EMBRYONIC_APPENDAGE_MORPHOGENESIS, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ZNF146_TARGET_GENES, BLANCO_MELO_INFLUENZA_A_INFECTION_A594_CELLS_DN, BLANCO_MELO_COVID19_SARS_COV_2_INFECTION_A594_CELLS_DN, DESCARTES_MAIN_FETAL_SATB2_LRRC7_POSITIVE_CELLS, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOMF_CIS_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), embryonic limb morphogenesis (GO:0030326)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
RNA polymerase II transcription regulatory region sequence-specific DNA binding2
regulation of DNA-templated transcription1
transcription by RNA polymerase II1
limb morphogenesis1
embryonic appendage morphogenesis1
cis-regulatory region sequence-specific DNA binding1
chromatin1
DNA-binding transcription factor activity1
regulation of transcription by RNA polymerase II1
transition metal ion binding1
double-stranded DNA binding1
sequence-specific DNA binding1
nucleic acid binding1
DNA binding1
cation binding1
chromosome1
cellular anatomical structure1
intracellular membrane-bounded organelle1

Protein interactions and networks

STRING

572 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
SP9ACRV1P26436883
SP9LIPNQ5VXI9792
SP9LRP5O75197582
SP9PCSK5Q92824547
SP9TMEM176BQ3YBM2542
SP9DNAAF10Q96MX6525
SP9DLX2Q07687503
SP9GSX2Q9BZM3474
SP9TSHZ1Q6ZSZ6437
SP9DLX1P56177436
SP9ETAA1Q9NY74423
SP9GSX1Q9H4S2409
SP9ASCL1P50553404
SP9STAT3P40763402
SP9VRTNQ9H8Y1384

IntAct

4 interactions, top by confidence:

ABTypeScore
Ppsi-mi:“MI:0914”(association)0.350
ATG16L1psi-mi:“MI:0914”(association)0.350
SP7IGF2BP3psi-mi:“MI:2364”(proximity)0.270

BioGRID (14): SP9 (Proximity Label-MS), SP9 (Proximity Label-MS), SP9 (Proximity Label-MS), SP9 (Proximity Label-MS), SP9 (Proximity Label-MS), SP9 (Proximity Label-MS), SP9 (Proximity Label-MS), SP9 (Proximity Label-MS), SP9 (Proximity Label-MS), SP9 (Proximity Label-MS), SP9 (Proximity Label-MS), SP9 (Proximity Label-MS), SP9 (Proximity Label-MS), SP9 (Proximity Label-MS)

ESM2 similar proteins: A0JC51, A5ABV9, B0X9H6, G5EGB2, O09100, O57311, O60481, O73689, O95409, P07247, P0CG40, P10070, P23769, P23824, P39768, P43694, P46152, P46684, P91623, Q00939, Q08369, Q0Q0E4, Q0VA40, Q0VGT2, Q15915, Q1A1A4, Q4V5A3, Q60987, Q61602, Q62520, Q62521, Q64HY3, Q6DJQ6, Q6P0J3, Q7TQ40, Q8JJC0, Q8N9L1, Q91660, Q91689, Q924Y4

Diamond homologs: A5ABV9, O08876, O14901, O70494, O89090, O89091, P08047, P0CG40, P41696, Q01714, Q02446, Q02447, Q0VA40, Q13351, Q22678, Q3SY56, Q5XGT8, Q62445, Q64HY3, Q64HY5, Q6BEB4, Q6NW96, Q6P0J3, Q8BMJ8, Q8IXZ3, Q8K1S5, Q8TDD2, Q8VI67, Q90WR8, Q9ESX2, Q9JHX2, Q9TZ64, A1C6L9, A1DH89, A2QCJ9, B0XSK6, B8NGC8, G4N3L5, K9GKQ6, O14335

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic4
Likely pathogenic2
Uncertain significance49
Likely benign3
Benign0

Top pathogenic / likely-pathogenic (6)

Variant IDHGVSClassification
1297467NM_001145250.2(SP9):c.1133A>G (p.Glu378Gly)Pathogenic
1297468NM_001145250.2(SP9):c.1216del (p.His406fs)Pathogenic
1297469NM_001145250.2(SP9):c.1192_1207dup (p.Arg403fs)Pathogenic
4813568NM_001145250.2(SP9):c.245C>A (p.Ser82Ter)Pathogenic
1297466NM_001145250.2(SP9):c.1133A>C (p.Glu378Ala)Likely pathogenic
4820605NM_001145250.2(SP9):c.1230_1231del (p.His410_Ile411insTer)Likely pathogenic

SpliceAI

168 predictions. Top by Δscore:

VariantEffectΔscore
2:174335110:CGGGG:Cdonor_loss1.0000
2:174335111:GGG:Gdonor_gain1.0000
2:174335112:GG:Gdonor_gain1.0000
2:174335112:GGG:Gdonor_gain1.0000
2:174335113:GG:Gdonor_gain1.0000
2:174335114:G:GAdonor_loss1.0000
2:174335114:G:GGdonor_gain1.0000
2:174335115:T:Gdonor_loss1.0000
2:174335109:TCGGG:Tdonor_gain0.9900
2:174335110:CGGG:Cdonor_gain0.9900
2:174335111:GGGG:Gdonor_gain0.9900
2:174336103:CTAG:Cacceptor_loss0.9800
2:174336104:TAGG:Tacceptor_loss0.9800
2:174336105:AGG:Aacceptor_loss0.9800
2:174336106:GGAA:Gacceptor_gain0.9800
2:174336100:A:AGacceptor_gain0.9700
2:174336105:A:AGacceptor_gain0.9700
2:174336106:G:GGacceptor_gain0.9700
2:174336105:AG:Aacceptor_gain0.9600
2:174336106:GG:Gacceptor_gain0.9600
2:174336106:GGA:Gacceptor_gain0.9600
2:174336092:T:Gacceptor_gain0.9400
2:174336091:A:AGacceptor_gain0.9300
2:174336097:C:Gacceptor_gain0.9300
2:174336101:C:Gacceptor_gain0.9300
2:174336096:A:AGacceptor_gain0.9100
2:174335917:A:AGdonor_gain0.8200
2:174336104:TAGGA:Tacceptor_gain0.8200
2:174336105:AGGAA:Aacceptor_gain0.8200
2:174336106:GGAAG:Gacceptor_gain0.8200

AlphaMissense

3104 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
2:174337100:T:AC339S1.000
2:174337100:T:CC339R1.000
2:174337101:G:AC339Y1.000
2:174337101:G:CC339S1.000
2:174337131:T:CL349P1.000
2:174337139:C:AH352N1.000
2:174337139:C:GH352D1.000
2:174337140:A:GH352R1.000
2:174337141:C:AH352Q1.000
2:174337141:C:GH352Q1.000
2:174337143:T:CL353P1.000
2:174337145:C:AR354S1.000
2:174337151:C:GH356D1.000
2:174337153:C:AH356Q1.000
2:174337153:C:GH356Q1.000
2:174337169:T:CF362L1.000
2:174337171:C:AF362L1.000
2:174337171:C:GF362L1.000
2:174337175:T:AC364S1.000
2:174337175:T:CC364R1.000
2:174337176:G:AC364Y1.000
2:174337176:G:CC364S1.000
2:174337177:C:GC364W1.000
2:174337190:T:AC369S1.000
2:174337190:T:CC369R1.000
2:174337191:G:AC369Y1.000
2:174337191:G:CC369S1.000
2:174337192:C:GC369W1.000
2:174337198:G:CK371N1.000
2:174337198:G:TK371N1.000

dbSNP variants (sampled 300 via entrez): RS1000267959 (2:174333694 T>C), RS1000297496 (2:174337594 G>A,T), RS1001373621 (2:174336790 G>A,C,T), RS1001770619 (2:174333314 C>A,T), RS1001824534 (2:174336356 C>T), RS1002902110 (2:174337899 A>G), RS1003088011 (2:174334895 C>T), RS1003369310 (2:174333925 G>A,C), RS1003443712 (2:174335193 C>T), RS1003827712 (2:174334834 C>A), RS1004390868 (2:174334605 C>T), RS1005897712 (2:174338752 A>G), RS1006073213 (2:174333219 C>G), RS1007353292 (2:174338960 A>C), RS1007363610 (2:174338378 TATC>T)

Disease associations

OMIM: gene MIM:621003 | disease phenotypes:

GenCC curated gene-disease

DiseaseClassificationInheritance
neurodevelopmental disorderStrongAutosomal dominant
complex neurodevelopmental disorderModerateAutosomal dominant

Mondo (3): intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

DescriptorNameTree numbers
D008607Intellectual DisabilityC10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886Neurodevelopmental DisordersF03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

ChemicalActions (top 5)PubMed papers
bisphenol Adecreases methylation1
ferrous chloridedecreases expression1
abrinedecreases expression1
jinfukangincreases expression, affects cotreatment1
Air Pollutantsaffects methylation, increases abundance1
Benzo(a)pyreneaffects methylation, decreases methylation1
Cisplatinaffects cotreatment, increases expression1
Nitrogen Dioxideaffects methylation, increases abundance1
Aflatoxin B1decreases methylation1
Particulate Matteraffects methylation, increases abundance1

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT04586348PHASE4UNKNOWNPrenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115PHASE4UNKNOWNDouble-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860PHASE4COMPLETEDGuanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479PHASE4RECRUITINGMetformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829PHASE4WITHDRAWNValbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198PHASE4NOT_YET_RECRUITINGDeutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102PHASE3COMPLETEDDexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079PHASE3COMPLETEDStudy of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480PHASE3RECRUITINGReducing Missed Appointments
NCT07377032PHASE3RECRUITINGTAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736PHASE3COMPLETEDClinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959PHASE2COMPLETEDSulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348PHASE2RECRUITINGSertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372PHASE2COMPLETEDSafety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302PHASE2COMPLETEDDown Syndrome Memantine Follow-up Study
NCT03862950PHASE2COMPLETEDA Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226PHASE2UNKNOWNStudy to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856PHASE2COMPLETEDEvaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191PHASE1COMPLETEDNeuroModulation Technique Treatment of Autism
NCT04475848PHASE1COMPLETEDA Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398PHASE1COMPLETEDIAMA-6 Oral Dose Study in Healthy Adults
NCT05273320PHASE1COMPLETEDClinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361PHASE1ENROLLING_BY_INVITATIONSensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764PHASE1COMPLETEDUse of MRI and cTBS for Catatonia in Autism
NCT06586827PHASE1COMPLETEDImpact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940PHASE1NOT_YET_RECRUITINGEscalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01783041PHASE2/PHASE3COMPLETEDEffect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385PHASE2/PHASE3RECRUITINGFetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098EARLY_PHASE1NOT_YET_RECRUITINGCentral Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783Not specifiedCOMPLETEDCYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504Not specifiedRECRUITINGStudying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784Not specifiedUNKNOWNHigh Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791Not specifiedCOMPLETEDNutrition and Pregnancy Intervention Study
NCT01942525Not specifiedUNKNOWNInfluence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170Not specifiedCOMPLETEDEtiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649Not specifiedACTIVE_NOT_RECRUITINGEnhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191Not specifiedTERMINATEDBiomarkers, Neurodevelopment and Preterm Infants
NCT02690675Not specifiedCOMPLETEDIron Supplement Effect on Child Development
NCT02694003Not specifiedCOMPLETEDBetter Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894Not specifiedCOMPLETEDFamily Networks (FaNs) for Children With Developmental Disorders and Delays