RFX7

Chr 15AD

regulatory factor X7

Also known as: MRD71, RFXDC2

NCBI Gene: 64864 ENSG00000181827 UniProt: Q2KHR2 OMIM: 612660

RFX7 encodes a transcription factor that activates target genes including PDCD4, PIK3IP1, MXD4, PNRC1, and RFX5, and functions in natural killer cell maintenance and neural tube ciliogenesis. Mutations cause autosomal dominant intellectual developmental disorder with behavioral abnormalities. This gene is highly constrained against loss-of-function variants (pLI=1.0, LOEUF=0.13), indicating intolerance to protein-truncating mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.131 OMIM phenotype

Clinical Summary— RFX7

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.

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ClinVar Variants

17 unique Pathogenic / Likely Pathogenic· 248 VUS of 359 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

1.60Z-score

OE missense 0.84 (0.78–0.89)

637 obs / 761.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.04 (0.02–0.13)

0≤0.351.4

Missense OE?0.84 (0.78–0.89)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 2 / 47.6Missense obs/exp: 637 / 761.2Syn Z: -0.25

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateRFX7-related neurodevelopmental disorder with autism and other behavioural abnormalitiesLOFAD

This gene — mechanism propensity

0.2199th %ile

GOF

0.1799th %ile

LOF

0.84top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 88% of P/LP variants are LoF · LOEUF 0.13

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

359 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic12

VUS248

Likely Benign75

Benign8

Conflicting3

Pathogenic

Likely Pathogenic

248

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	1	0	0	5
Likely Pathogenic	11	1	0	0	12
VUS	12	231	4	1	248
Likely Benign	0	59	3	13	75
Benign	0	2	3	3	8
Conflicting	—				3
Total	27	294	10	17	351

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap RFX7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →