RFX7

Chr 15AD

regulatory factor X7

Also known as: MRD71, RFXDC2

NCBI Gene: 64864ENSG00000181827UniProt: Q2KHR2

RFX7 is a member of the regulatory factor X (RFX) family of transcription factors (see RFX1, MIM 600006) (Aftab et al., 2008 [PubMed 18673564]).[supplied by OMIM, Mar 2009]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalitiesMIM #620330
AD
357
ClinVar variants
32
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RFX7
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 246 VUS of 357 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.13LOEUF
pLI 1.000
Z-score 6.13
OE 0.04 (0.02–0.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.60Z-score
OE missense 0.84 (0.78–0.89)
637 obs / 761.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.04 (0.02–0.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.78–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 2 / 47.6Missense obs/exp: 637 / 761.2Syn Z: -0.25

ClinVar Variant Classifications

357 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic10
VUS246
Likely Benign70
Benign7
Conflicting2
22
Pathogenic
10
Likely Pathogenic
246
VUS
70
Likely Benign
7
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
19
0
22
Likely Pathogenic
7
1
2
0
10
VUS
6
223
16
1
246
Likely Benign
0
54
4
12
70
Benign
0
2
3
2
7
Conflicting
—2
Total152814415357

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RFX7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

RFX7-related neurodevelopmental disorder with autism and other behavioural abnormalities

moderate
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
frameshift variantstop gainedmissense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities

MIM #620330

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior.
Harris HK et al.·Genet Med
2021
Expanding the clinical phenotype and variant spectrum associated with RFX7.
Sisroe T et al.·Am J Med Genet A
2024Case report
Phenotype expansion and neurological manifestations of neurobehavioural disease caused by a variant in RFX7.
Ledger ML et al.·Eur J Med Genet
2023Case report
The landscape of human p53-regulated long non-coding RNAs reveals critical host gene co-regulation.
Fischer M et al.·Mol Oncol
2023
Identification of RFX5 as prognostic biomarker and associated with immune infiltration in stomach adenocarcinoma.
Guo L et al.·Eur J Med Res
2022
Thymocyte regulatory variant alters transcription factor binding and protects from type 1 diabetes in infants.
Sandholm N et al.·Sci Rep
2022
Deciphering the mechanisms of CC-122 resistance in DLBCL via a genome-wide CRISPR screen.
Mo Z et al.·Blood Adv
2021Functional
Knowledge-driven binning approach for rare variant association analysis: application to neuroimaging biomarkers in Alzheimer's disease.
Kim D et al.·BMC Med Inform Decis Mak
2017
A multigene predictor of metastatic outcome in early stage hormone receptor-negative and triple-negative breast cancer.
Yau C et al.·Breast Cancer Res
2010
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools