Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities

Summary

Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities (MONDO:0957228) is a disease caused by RFX7 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: RFX7 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 29

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities
Mondo ID	MONDO:0957228
OMIM	620330
DOID	DOID:0061044
UMLS	C5830437
MedGen	1841073
Is cancer (heuristic)	no

Data availability: 29 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › intellectual disability, autosomal dominant › intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities

Related subtypes (28): intellectual disability, autosomal dominant 1, intellectual disability, autosomal dominant 3, intellectual disability, autosomal dominant 4, intellectual disability, autosomal dominant 5, intellectual disability, autosomal dominant 6, intellectual disability, autosomal dominant 2, neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, intellectual disability, autosomal dominant 9, intellectual disability, autosomal dominant 10, intellectual disability, autosomal dominant 11, intellectual disability, autosomal dominant 24, intellectual disability, autosomal dominant 38, intellectual disability, autosomal dominant 39, intellectual disability, autosomal dominant 40, intellectual disability, autosomal dominant 42, autosomal dominant non-syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 65, intellectual developmental disorder, autosomal dominant 69, intellectual developmental disorder, autosomal dominant 66, intellectual developmental disorder, autosomal dominant 64, intellectual developmental disorder, autosomal dominant 67, intellectual developmental disorder, autosomal dominant 68, autosomal dominant syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 70, intellectual developmental disorder, autosomal dominant 72, intellectual developmental disorder, autosomal dominant 74, intellectual developmental disorder, autosomal dominant 75, intellectual developmental disorder, autosomal dominant 76

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

29 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 5 likely pathogenic, 4 pathogenic, 2 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1705979	NM_022841.7(RFX7):c.3082C>T (p.Pro1028Ser)	RFX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1712559	NM_022841.7(RFX7):c.3083C>T (p.Pro1028Leu)	RFX7	Pathogenic	criteria provided, multiple submitters, no conflicts
2499502	NM_022841.7(RFX7):c.3032del (p.Ser1011fs)	RFX7	Pathogenic	no assertion criteria provided
2499503	NM_022841.7(RFX7):c.2718C>A (p.Tyr906Ter)	RFX7	Pathogenic	no assertion criteria provided
2507306	NM_022841.7(RFX7):c.2459_2462del (p.Val820fs)	RFX7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3376854	NM_022841.7(RFX7):c.1399_1400del (p.Met467fs)	RFX7	Pathogenic	criteria provided, single submitter
3897629	NM_022841.7(RFX7):c.1464del (p.Lys490fs)	RFX7	Likely pathogenic	criteria provided, single submitter
4076373	NM_022841.7(RFX7):c.100dup (p.Val34fs)	RFX7	Likely pathogenic	criteria provided, single submitter
4076377	NM_022841.7(RFX7):c.45_55del (p.His16fs)	RFX7	Likely pathogenic	criteria provided, single submitter
4819144	NM_022841.7(RFX7):c.2680_2681dup (p.Met894fs)	RFX7	Likely pathogenic	criteria provided, single submitter
4845504	NM_022841.7(RFX7):c.2236C>T (p.Gln746Ter)	RFX7	Likely pathogenic	criteria provided, single submitter
3677129	NM_022841.7(RFX7):c.3085A>G (p.Ile1029Val)	RFX7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4081935	NC_000015.10:g.56243115_56373514dup	LOC130057120	Uncertain significance	no assertion criteria provided
2462070	NM_022841.7(RFX7):c.2113dup (p.Thr705fs)	RFX7	Uncertain significance	criteria provided, single submitter
2575770	NM_022841.7(RFX7):c.739T>C (p.Phe247Leu)	RFX7	Uncertain significance	criteria provided, multiple submitters, no conflicts
2628081	NM_022841.7(RFX7):c.671G>A (p.Arg224His)	RFX7	Uncertain significance	criteria provided, single submitter
2689867	NM_022841.7(RFX7):c.2147G>C (p.Ser716Thr)	RFX7	Uncertain significance	criteria provided, single submitter
3065672	NM_022841.7(RFX7):c.3781_3783del (p.Asn1261del)	RFX7	Uncertain significance	criteria provided, single submitter
3376358	NM_022841.7(RFX7):c.94G>T (p.Ala32Ser)	RFX7	Uncertain significance	criteria provided, single submitter
3775696	NM_022841.7(RFX7):c.812-39A>T	RFX7	Uncertain significance	criteria provided, single submitter
4076374	NM_022841.7(RFX7):c.1388C>T (p.Pro463Leu)	RFX7	Uncertain significance	criteria provided, single submitter
4076375	NM_022841.7(RFX7):c.1544C>G (p.Ser515Cys)	RFX7	Uncertain significance	criteria provided, single submitter
4076376	NM_022841.7(RFX7):c.279-6T>C	RFX7	Uncertain significance	criteria provided, single submitter
4076378	NM_022841.7(RFX7):c.62C>T (p.Pro21Leu)	RFX7	Uncertain significance	criteria provided, single submitter
4079859	NM_022841.7(RFX7):c.1789G>C (p.Asp597His)	RFX7	Uncertain significance	criteria provided, single submitter
4292122	NM_022841.7(RFX7):c.811G>C (p.Gly271Arg)	RFX7	Uncertain significance	criteria provided, single submitter
4531503	NM_022841.7(RFX7):c.310C>T (p.Gln104Ter)	RFX7	Uncertain significance	criteria provided, single submitter
4796012	NM_022841.7(RFX7):c.1031T>G (p.Leu344Arg)	RFX7	Uncertain significance	criteria provided, single submitter
4795896	NM_022841.7(RFX7):c.1621C>G (p.Pro541Ala)	RFX7	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
RFX7	Strong	Autosomal dominant	intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities	2

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RFX7	HGNC:25777	ENSG00000181827	Q2KHR2	DNA-binding protein RFX7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RFX7	DNA-binding protein RFX7	Transcription factor.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RFX7	Other/Unknown	no		DNA-bd_RFX, WH-like_DNA-bd_sf, WH_DNA-bd_sf

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
skeletal muscle tissue of rectus abdominis	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RFX7	263	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, cortical plate, upper leg skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RFX7	785

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RFX7	Q2KHR2	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of transcription by RNA polymerase II	1	14.9×	0.086	RFX7
regulation of transcription by RNA polymerase II	1	11.7×	0.086	RFX7

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RFX7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RFX7

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RFX7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.