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Atlas / Disease / Scoliosis, isolated, susceptibility to, 1

Scoliosis, isolated, susceptibility to, 1

disease
On this page

Also known as IS1scoliosis, idiopathic 1

Summary

Scoliosis, isolated, susceptibility to, 1 (MONDO:0008419) is a disease with 7 cohort genes.

At a glance

  • Cohort genes: 7
  • ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namescoliosis, isolated, susceptibility to, 1
Mondo IDMONDO:0008419
OMIM181800
UMLSC2700406
MedGen438003
Is cancer (heuristic)no

Also known as: IS1 · scoliosis, idiopathic 1 · scoliosis, isolated, susceptibility to, 1

Data availability: 10 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › scoliosis, isolated, susceptibility to › scoliosis, isolated, susceptibility to, 1

Related subtypes (5): scoliosis, isolated, susceptibility to, 2, scoliosis, isolated, susceptibility to, 3, scoliosis, isolated, susceptibility to, 4, scoliosis, isolated, susceptibility to, 5, scoliosis, isolated, susceptibility to, 6

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

10 retrieved; paginated sample, class counts are floors:

5 pathogenic, 3 uncertain significance, 1 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVarVariant (HGVS)GeneClassificationReview
3899918NM_000125.4(ESR1):c.453-351A>GESR1Pathogeniccriteria provided, single submitter
427639NM_002749.4(MAPK7):c.886G>A (p.Ala296Thr)MAPK7Pathogenicno assertion criteria provided
427640NM_002749.4(MAPK7):c.1760C>T (p.Pro587Leu)MAPK7Pathogenicno assertion criteria provided
427641NM_002749.4(MAPK7):c.1943C>T (p.Pro648Leu)MAPK7Pathogenicno assertion criteria provided
3899921NM_001099271.2(POC5):c.1211C>T (p.Ser404Leu)POC5Pathogeniccriteria provided, single submitter
1225367NM_013312.3(HOOK2):c.1464C>G (p.His488Gln)HOOK2Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
4082084NM_032532.3(FNDC1):c.391+82A>GFNDC1Uncertain significancecriteria provided, single submitter
2444480NM_001142966.3(GREB1L):c.2947G>A (p.Gly983Ser)GREB1LUncertain significancecriteria provided, multiple submitters, no conflicts
2444481NM_001142966.3(GREB1L):c.2321T>A (p.Leu774Gln)GREB1LUncertain significancecriteria provided, single submitter
129415NM_198525.3(KIF7):c.3345C>G (p.His1115Gln)KIF7Benign/Likely benigncriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
KIF7Orphanet:166024Multiple epiphyseal dysplasia-macrocephaly-facial dysmorphism syndrome
KIF7Orphanet:2189Hydrolethalus
KIF7Orphanet:2754Orofaciodigital syndrome type 6
KIF7Orphanet:36Acrocallosal syndrome
GREB1LOrphanet:1848Renal agenesis, bilateral
GREB1LOrphanet:93100Renal agenesis, unilateral
ESR1Orphanet:785Estrogen resistance syndrome

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence7

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
HOOK2HGNC:19885ENSG00000095066Q96ED9Protein Hook homolog 2clinvar
FNDC1HGNC:21184ENSG00000164694Q4ZHG4Fibronectin type III domain-containing protein 1clinvar
POC5HGNC:26658ENSG00000152359Q8NA72Centrosomal protein POC5clinvar
KIF7HGNC:30497ENSG00000166813Q2M1P5Kinesin-like protein KIF7clinvar
GREB1LHGNC:31042ENSG00000141449Q9C091GREB1-like proteinclinvar
ESR1HGNC:3467ENSG00000091831P03372Estrogen receptorclinvar
MAPK7HGNC:6880ENSG00000166484Q13164Mitogen-activated protein kinase 7clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
HOOK2Protein Hook homolog 2Component of the FTS/Hook/FHIP complex (FHF complex).
FNDC1Fibronectin type III domain-containing protein 1May be an activator of G protein signaling.
POC5Centrosomal protein POC5Essential for the assembly of the distal half of centrioles, required for centriole elongation.
KIF7Kinesin-like protein KIF7Essential for hedgehog signaling regulation: acts both as a negative and positive regulator of sonic hedgehog (Shh) and Indian hedgehog (Ihh) pathways, acting downstream of SMO, through both SUFU-dependent and -independent mechanisms.
GREB1LGREB1-like proteinPlays a major role in early metanephros and genital development.
ESR1Estrogen receptorNuclear hormone receptor.
MAPK7Mitogen-activated protein kinase 7Plays a role in various cellular processes such as proliferation, differentiation and cell survival.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.43

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Nuclear receptor155.1×0.072
Antibody/Immunoglobulin14.2×0.302
Kinase14.0×0.302
Other/Unknown41.0×0.626

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
HOOK2Other/UnknownnoCH_dom, Hook_C, CH_dom_sf
FNDC1Antibody/ImmunoglobulinyesFN3_dom, Ig-like_fold, FN3_sf
POC5Other/UnknownnoPOC5
KIF7Other/UnknownnoKinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
GREB1LOther/UnknownnoGREB1, GREB1_N, GREB1-like_C
ESR1Nuclear receptoryesNucl_hrmn_rcpt_lig-bd, Estr_rcpt, Znf_hrmn_rcpt
MAPK7Kinaseyes2.7.11.24Prot_kinase_dom, MAP_kinase_CS, Ser/Thr_kinase_AS

Expression context

Cohort genes with no expression data: 0.

5 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)7
unknown0

Top tissues across cohort

TissueCohort genes
apex of heart1
left lobe of thyroid gland1
right lobe of thyroid gland1
cartilage tissue1
synovial joint1
tendon of biceps brachii1
oocyte1
primordial germ cell in gonad1
secondary oocyte1
cardiac muscle of right atrium1
kidney epithelium1
left ventricle myocardium1
buccal mucosa cell1
gastrocnemius1
male germ line stem cell (sensu Vertebrata) in testis1
cervix epithelium1
mammalian vulva1
oviduct epithelium1
ganglionic eminence1
lower esophagus mucosa1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
HOOK2233ubiquitousmarkerright lobe of thyroid gland, apex of heart, left lobe of thyroid gland
FNDC1183broadmarkertendon of biceps brachii, synovial joint, cartilage tissue
POC5224ubiquitousyessecondary oocyte, oocyte, primordial germ cell in gonad
KIF7165ubiquitousyeskidney epithelium, cardiac muscle of right atrium, left ventricle myocardium
GREB1L184broadmarkerbuccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, gastrocnemius
ESR1216broadmarkeroviduct epithelium, cervix epithelium, mammalian vulva
MAPK7219ubiquitousmarkerlower esophagus mucosa, ganglionic eminence, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

SymbolInteractor count
ESR112,382
MAPK74,364
HOOK21,879
KIF71,655
POC51,147
FNDC1897
GREB1L637

Intra-cohort edges

ABSources
ESR1GREB1Lintact
HOOK2POC5intact

Structural data

PDB: 3 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
ESR1P03372478
MAPK7Q1316414
KIF7Q2M1P55

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
HOOK2Q96ED982.81
GREB1LQ9C09172.90
POC5Q8NA7265.76
FNDC1Q4ZHG454.19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 63. Enrichment computed across 7 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Signalling to ERK511903.3×0.029MAPK7
RUNX1 regulates estrogen receptor mediated transcription1634.4×0.029ESR1
RUNX1 regulates transcription of genes involved in WNT signaling1634.4×0.029ESR1
ERKs are inactivated1292.8×0.029MAPK7
Gastrin-CREB signalling pathway via PKC and MAPK1292.8×0.029MAPK7
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors1253.8×0.029ESR1
ERK/MAPK targets1223.9×0.029MAPK7
Developmental Lineage of Mammary Gland Alveolar Cells1211.5×0.029ESR1
Mitochondrial unfolded protein response (UPRmt)1200.3×0.029ESR1
MAPK targets/ Nuclear events mediated by MAP kinases1181.3×0.029MAPK7
Developmental Lineage of Mammary Gland Luminal Epithelial Cells1152.3×0.029ESR1
Nuclear signaling by ERBB41115.3×0.029ESR1
Nuclear Events (kinase and transcription factor activation)1115.3×0.029MAPK7
SUMOylation of intracellular receptors1112.0×0.029ESR1
MAP kinase activation1102.9×0.029MAPK7
Ovarian tumor domain proteases192.8×0.029ESR1
RET signaling186.5×0.029MAPK7
Interleukin-17 signaling184.6×0.029MAPK7
Toll Like Receptor 10 (TLR10) Cascade171.8×0.029MAPK7
Toll Like Receptor 5 (TLR5) Cascade171.8×0.029MAPK7
MyD88 cascade initiated on plasma membrane168.0×0.029MAPK7
Nuclear Receptor transcription pathway166.8×0.029ESR1
Signaling by NTRK1 (TRKA)165.6×0.029MAPK7
Toll Like Receptor 3 (TLR3) Cascade164.5×0.029MAPK7
TRIF (TICAM1)-mediated TLR4 signaling163.4×0.029MAPK7
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation163.4×0.029MAPK7
MyD88 dependent cascade initiated on endosome163.4×0.029MAPK7
MyD88-independent TLR4 cascade161.4×0.029MAPK7
Toll Like Receptor 7/8 (TLR7/8) Cascade161.4×0.029MAPK7
Signaling by Hedgehog161.4×0.029KIF7

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
negative regulation of smooth muscle cell apoptotic process2468.1×6e-04ESR1, MAPK7
uterus development2267.5×1e-03GREB1L, ESR1
regulation of epithelial cell apoptotic process12808.7×0.011ESR1
negative regulation of centriole elongation11404.3×0.012POC5
positive regulation of nitric-oxide synthase activity1936.2×0.012ESR1
prostate epithelial cord elongation1936.2×0.012ESR1
mammary gland branching involved in pregnancy1702.2×0.012ESR1
paramesonephric duct development1702.2×0.012GREB1L
centriole elongation1702.2×0.012POC5
antral ovarian follicle growth1561.7×0.012ESR1
steroid hormone receptor signaling pathway1561.7×0.012ESR1
regulation of branching involved in prostate gland morphogenesis1561.7×0.012ESR1
mesonephric duct development1561.7×0.012GREB1L
epithelial cell proliferation involved in mammary gland duct elongation1468.1×0.013ESR1
negative regulation of response to cytokine stimulus1468.1×0.013MAPK7
cardiac ventricle development1401.2×0.013GREB1L
prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis1401.2×0.013ESR1
nuclear receptor-mediated steroid hormone signaling pathway1351.1×0.013ESR1
cellular response to laminar fluid shear stress1351.1×0.013MAPK7
negative regulation of heterotypic cell-cell adhesion1312.1×0.014MAPK7
epithelial cell development1255.3×0.015ESR1
regulation of toll-like receptor signaling pathway1255.3×0.015ESR1
vagina development1255.3×0.015ESR1
protein localization to perinuclear region of cytoplasm1234.1×0.016HOOK2
positive regulation of protein metabolic process1165.2×0.019MAPK7
mammary gland alveolus development1165.2×0.019ESR1
cytoskeleton-dependent intracellular transport1156.0×0.019HOOK2
negative regulation of calcineurin-NFAT signaling cascade1156.0×0.019MAPK7
cellular response to estrogen stimulus1156.0×0.019ESR1
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway1156.0×0.019MAPK7

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 5

Druggability breadth: 3 of 7 evidence-associated genes (43%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
ESR1CANDESARTAN CILEXETIL
MAPK7FEDRATINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
ESR11624
MAPK7194
HOOK200
FNDC100
POC500
KIF700
GREB1L00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
CANDESARTAN CILEXETIL4ESR1
DIENESTROL4ESR1
BEXAROTENE4ESR1
VARENICLINE4ESR1
ACETOPHENAZINE4ESR1
ARIPIPRAZOLE4ESR1
RALOXIFENE HYDROCHLORIDE4ESR1
NORETHINDRONE4ESR1
TRIMETREXATE4ESR1
ESTRADIOL ACETATE4ESR1
ETHYLESTRENOL4ESR1
ETHYNODIOL DIACETATE4ESR1
CHLOROTRIANISENE4ESR1
ESTRADIOL CYPIONATE4ESR1
MESTRANOL4ESR1
QUINESTROL4ESR1
RIBOFLAVIN 5’-PHOSPHATE4ESR1
ESTETROL ANHYDROUS4ESR1
OXYBUTYNIN4ESR1
MILTEFOSINE4ESR1
MIFEPRISTONE4ESR1
LENVATINIB4ESR1
CLOFAZIMINE4ESR1
BUTOCONAZOLE4ESR1
MOLSIDOMINE4ESR1
ESTRADIOL4ESR1
FULVESTRANT4ESR1
ERTAPENEM4ESR1
TOLTERODINE4ESR1
NORETHYNODREL4ESR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

SymbolAssaysType breakdown
ESR12,435Binding:2037, Functional:363, ADMET:35
MAPK7260Binding:260
KIF75Binding:5

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
MAPK72.7.11.24mitogen-activated protein kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

SymbolChEMBL assays
ESR12,435
MAPK7260

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

CompoundMax phaseCohort target (bioactivity)
CANDESARTAN CILEXETIL4ESR1
DIENESTROL4ESR1
BEXAROTENE4ESR1
VARENICLINE4ESR1
ACETOPHENAZINE4ESR1
ARIPIPRAZOLE4ESR1
RALOXIFENE HYDROCHLORIDE4ESR1
NORETHINDRONE4ESR1
TRIMETREXATE4ESR1
ESTRADIOL ACETATE4ESR1
ETHYLESTRENOL4ESR1
ETHYNODIOL DIACETATE4ESR1
CHLOROTRIANISENE4ESR1
ESTRADIOL CYPIONATE4ESR1
MESTRANOL4ESR1
QUINESTROL4ESR1
RIBOFLAVIN 5’-PHOSPHATE4ESR1
ESTETROL ANHYDROUS4ESR1
OXYBUTYNIN4ESR1
MILTEFOSINE4ESR1
MIFEPRISTONE4ESR1
LENVATINIB4ESR1
CLOFAZIMINE4ESR1
BUTOCONAZOLE4ESR1
MOLSIDOMINE4ESR1
ESTRADIOL4ESR1
FULVESTRANT4ESR1
ERTAPENEM4ESR1
TOLTERODINE4ESR1
NORETHYNODREL4ESR1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)2ESR1, MAPK7
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug1FNDC1
EDifficult family or no structure, no drug4HOOK2, POC5, KIF7, GREB1L

Undrugged target profiles

5 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

SymbolChEMBL assaysDrugged partners (top 3)
HOOK20—
FNDC10—
POC50—
KIF75—
GREB1L0—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
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Sources 67

This page pulls from 67 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot